bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 8 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 8. Model parameters informed from experimental data. A) The model’s death rate was determined by treating MTA cells with lethal doses of 4-H-cyclophophamide and doxorubicin and observing that the cell population halves every 2.5 days, n=1 per condition. Cells were incubated with drugs for 3 days (represented by yellow bar) before being washed off and replaced with drug-free media. B) The model’s treated growth rate was determined by treating MTA cells with the same drug concentrations used in the concurrent vs sequential dosing experiments and observing that cells double every 2.5 days, n=1 per condition. Cells were incubated with drugs for 3 days (represented by yellow bar) before being washed off and replaced with drug-free media. C) At each simulated drug treatment (marked with yellow triangles), the model calculates the fraction of cells that will survive and the fraction that will die. Each respective cell population is modelled as growing or dying at the experimentally determined rates. Total live cell count is calculated by adding the number of growing cells with the number of dying cells over time. D) 4-H-cyclophosphamide yields about 20% viability and doxorubicin yields about 40% viability at 13% Csustained, the concentration of drug that was used in the concurrent vs sequential administration experiments (2 μM and 20 nM respectively), n=8 per condition. E) To convert experimental concentrations to dose values for the model, the corresponding dose values at 20% and 40% viability were estimated to be 1.8 for doxorubicin and 2.6 for 4-H-cyclophosphamide. F) The CH isobologram created by the model matches the experimentally determined isobologram for MTA cells in Supplemental Figure 2b when the drug interaction term is set to a sub-additive value of i = -0.8. G) Model outputs of tumor cell populations over time were fit to the experimental data to fit the level of ultrasensitivity (β = 0.4) and the level of heterogeneity in drug sensitivity (σ = 0.42).
Supplementary Figure 4 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 4. Drug interactions in CHOP using MuSyC method to distinguish potency and efficacy shifts. A) The MuSyC method analyzes drug combination effects to distinguish between shifts in potency and shifts in efficacy. Shifts in potency from the Bliss model (orange) to observed data (blue) are represented by parameter A, where positive values indicate superior potency and negative values indicate inferior potency. Changes in efficacy are represented by parameter B, where positive values indicate greater inhibition, and negative values indicate less inhibition. B) Example of method for a drug combination with lower efficacy than predicted by the Bliss model. The interaction model (red) is fit from the Bliss model to the experimental data across the length of the curve. The quadrant plot shows the A and B parameters that confer the best fit determined by sum of squares errors. Stronger fits are colored darker blue and the best fit is marked in red. Data shows drug combination CHOP in SU-DHL-1 T-Cell lymphoma cell line, n=8. C) Example of method for a drug combination with higher efficacy than Bliss model predicts. Data shows drug combination leuocorovin-fluorouracil-irinotecan in Lovo Colorectal cancer cell line, n=8. D) Shifts in potency and efficacy for all 11 combinations of agents in CHOP, for each of four Peripheral T-Cell Lymphoma cell lines: KHYG-1, SU-DHL-1, Ki-JK, MTA. Yellow region marks a two-fold difference in potency or efficacy compared with the ‘no interaction’ null hypothesis. Error bars are 95% confidence intervals, n=8.
Supplementary Figure 3 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 3. Analysis of drug pairs, triplets, and quadruplet CHOP confirms antagonistic interactions by the Bliss Independence model. A) Effect of CHOP combination measured at concentrations from 0 to 200% of Csustained, compared with Bliss Independence model computed from monotherapy effects, in four PTCL cell lines: KHYG-1, Ki-JK, MTA, SU-DHL-1. Blue shading represents 95% confidence interval (n=8 replicates). B) Relationship between observed cell viability, and predicted viability from Bliss Independence model, for all possible pairs, triplets, and quadruplets of drugs in CHOP across four PTCL cell lines (n=237 points across concentration range up to 500% Csustained; each point is an average of 8 measurements). All combinations containing antagonistic pairs CH or HO are colored in blue; all other combinations in red. Lines of best fit show that, as a group, combinations containing the drug pairs CH or HO (blue line) are antagonistic compared with the Bliss independence model (black line) (P = 6×10-34, Student’s t-test, n=117), and also more antagonistic than all combinations without CH or HO (red line) (P = 3×10-14, Student’s t-test, n=237). Overall, all CHOP measurements (blue and red combined) are antagonistic compared with the Bliss independence model (black line), with an average slope of 0.79 (P = 7×10-35, Student’s t-test, n=237). C) Histogram depicting the difference in observed and expected log-kills (-log10(relative viability) for all interactions involving CH or HO (blue), and all remaining interactions (red)).
Supplementary Figure 2 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 2. Isobologram analysis shows antagonism between CH and HO in the CHOP regimen for Peripheral T-Cell Lymphoma. A) Left: shapes of equal-effect contour lines (isoboles) reveal non-additive drug interactions (Palmer et al.)9. Right: Cell viability is measured across an 11x11 concentration gradient to graph isobolograms. B) CH, HO, and CO drug interactions in four Peripheral T-Cell Lymphoma (PTCL) cell lines: KHYG-1, Ki-JK, MTA, SU-DHL-1 (n=4 replicates per plot). White contour lines highlight 50%, 20%, and 5% relative viability. Green dots mark a clinically relevant concentration, Csustained (the average plasma concentration in humans 6 hours after administration12). C) CH and HO pairwise drug interactions in three additional PTCL cell lines: SMZ-1, MOT-N1, DL-40 (n=4 replicates per plot).
Supplementary Figure 10 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 10. Combinations of drugs with varied mechanisms applied to the linear-quadratic model. We present here a preliminary investigation of how the linear-quadratic model (LQ) could have different implications if multiple drugs exert more distinct mechanisms of killing. Different drugs may exhibit different parameter values for α and β in the LQ model, but a further complexity is whether the quadratic terms are shared or distinct, which is compared here. (A) In this article, we have modelled cyclophosphamide and doxorubicin as both causing DNA damage and jointly adding to the accumulation of damage that is represented by the ‘quadratic’ term in the LQ model. When this applies to a hypothetical combination of drugs A+B, their combined dose can reach the ultrasensitive region of response more readily. Mathematically, the sum of drugs’ effects is squared. Without formally introducing drug-drug interaction, this equation results in an isobologram plot showing drugs A+B to be additive. (B) If drugs with highly distinct mechanisms of action are combined, their forms of damage may not jointly add up in the quadratic term of the LQ model. It may instead be justified to introduce distinct quadratic terms for each drug. Interestingly, even without formally introducing drug-drug interaction, such an equation leads to an isobologram plot that exhibits antagonistic (or sub-additive) interaction, even though the effect of the drug combination has been modelled as precisely additive. This arises because a combination of two half-doses is inferior to a full-dose of either single drug, because neither single drug dose extends as far into the ‘ultrasensitive’ region of response.
Supplementary Table S3 from Loss of the DNA Repair Gene RNase H2 Identifies a Unique Subset of DDR-Deficient Leiomyosarcomas
Authors: Nakazawa Michael S. , Silverman Ian M. , Rimkunas Victoria , Veloso Artur , Glodzik Dominik , Johnson Adrienne , Ohsumi Toshiro K. , Patel Shreyaskumar R. , Conley Anthony P. , Roland Christina L. , Soliman Pamela T. , Beird Hannah C. , Wu Chia-Chin , Ingram Davis R. , Lazcano Rossana , Song Dawon , Wani Khalida M. , Lazar Alexander J. , Yap Timothy A. , Wang Wei-Lien , Livingston J. Andrew
Published: July 2024

SNiPDx results of U-LMS and ST-LMS samples in the MDACC cohort, with RNase H2 IHC status also reported.
Data from Loss of the DNA Repair Gene RNase H2 Identifies a Unique Subset of DDR-Deficient Leiomyosarcomas
Authors: Nakazawa Michael S. , Silverman Ian M. , Rimkunas Victoria , Veloso Artur , Glodzik Dominik , Johnson Adrienne , Ohsumi Toshiro K. , Patel Shreyaskumar R. , Conley Anthony P. , Roland Christina L. , Soliman Pamela T. , Beird Hannah C. , Wu Chia-Chin , Ingram Davis R. , Lazcano Rossana , Song Dawon , Wani Khalida M. , Lazar Alexander J. , Yap Timothy A. , Wang Wei-Lien , Livingston J. Andrew
Published: July 2024

Abstract
Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR-targeted treatments. Therefore, we designed a protein- and genomic-based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS; 30%, 39/102). In the TCGA database, RNASEH2B homozygous deletions (HomDels) were found in 6% (5/80) of LMS cases, with a higher proportion in U-LMS (15%; 4/27) compared with ST-LMS (2%; 1/53). Using the SNiPDx targeted-NGS sequencing assay to detect biallelic loss of function in select DDR-related genes, we found RNASEH2B HomDels in 54% (19/35) of U-LMS cases with RNase H2 loss by IHC, and 7% (3/43) HomDels in RNase H2 intact cases. No RNASEH2B HomDels were detected in ST-LMS. In U-LMS patient cohort (n = 109), no significant overall survival difference was seen in patients with RNase H2 loss versus intact, or RNASEH2B HomDel (n = 12) versus Non-HomDel (n = 37). The overall diagnostic accuracy, sensitivity, and specificity of RNase H2 IHC for detecting RNA-SEH2B HomDels in U-LMS was 76%, 93%, and 71%, respectively, and it is being developed for future predictive biomarker driven clinical trials targeting DDR in U-LMS.
Supplementary Table S3 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Table S3. Antibody information.
Supplementary Figure S4 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Figure S4. Notch pathway is not altered upon chemotherapy drug treatment.
Supplementary Table 1 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Table 1 shows the general description of patients
Supplementary Figure S3 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Figure S3. HUWE1 mediates ASCL1 degradation during mitosis.
Figure S5 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Figure S5 shows the extended data of "SLUG reversed the stemness properties and immune escape induced by ALKBH5"
Supplementary Figure S2 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Figure S2. Phosphorylation of ASCL1 reduces its protein stability by CDK2-CyclinA2.
Figure S4 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Figure S4 shows the extended data of "ALKBH5-mediated m6A demethylation in 3’UTR region of SNAI2 mRNA is recognized by YTHDF2"
Figure S2 from Hepatitis B Virus–Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape
Authors: Meng Yuting , Shu Zheyue , Wang Xueyao , Hong Liang , Wang Baohua , Jiang Jingjing , He Kangxin , Cao Qingyi , Shi Fan , Wang Hai , Gong Lan , Diao Hongyan
Published: July 2024

Supplementary Figure S2 shows the extended data of "HBV up-regulated ALKBH5 in HBV-positive HCC"
Supplementary Table S1 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Differentially expressed genes between LG-, PRI- and REC-GVC
Supplementary Table S5 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

The epigenomic analysis of transcription factor genes repressed by EWSR1::FLI1
Supplementary Table S4 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

The epigenomic analysis of TC-32 EWS cells
Supplementary Figure S6 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Supplementary Figure S6. ASPN knockdown and validation in cultured GVC
Supplementary Table S2 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

RNA-seq analysis of EWSR1::FLI1-depleted EWS cells
Supplementary Table S1 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

Reagents and resources
Supplementary Figure S4 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

ETS1 promotes the migration of EWS cells and regulates the expression of TENSIN3
Supplementary Figure S3 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

Ectopic expression of ETS1 has transcriptome-wide effects.
Supplementary Figure S1 from Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway
Authors: Zhong Ying , Kang Hui , Ma Ziqing , Li Jiayu , Qin Zixi , Zhang Zixuan , Li Peiwen , Zhong Ying , Wang Lihui
Published: July 2024

Establishment of glioma cell lines with VASN overexpressed or knocked down
Data from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Abstract
A key feature distinguishing high-grade glioma (HG) from low-grade glioma (LG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor-associated vasculature from HG is molecularly and functionally distinct from normal brain vasculature and expresses higher levels of protumorigenic factors that promote glioma growth and progression. However, it remains unclear whether vessels from LG also express protumorigenic factors, and to what extent they functionally contribute to glioma growth. Here, we profile the transcriptomes of glioma-associated vascular cells (GVC) from IDH-mutant (mIDH) LG and IDH-wild-type (wIDH) HG and show that they exhibit significant molecular and functional differences. LG-GVC show enrichment of extracellular matrix–related gene sets and sensitivity to antiangiogenic drugs, whereas HG-GVC display an increase in immune response–related gene sets and antiangiogenic resistance. Strikingly, conditioned media from LG-GVC inhibits the growth of wIDH glioblastoma cells, whereas HG-GVC promotes growth. In vivo cotransplantation of LG-GVC with tumor cells reduces growth, whereas HG-GVC enhances tumor growth in orthotopic xenografts. We identify ASPORIN (ASPN), a small leucine-rich repeat proteoglycan, highly enriched in LG-GVC as a growth suppressor of wIDH glioblastoma cells in vitro and in vivo. Together, these findings indicate that GVC from LG and HG are molecularly and functionally distinct and differentially regulate tumor growth.

Implications: This study demonstrated that vascular cells from IDH-mutant LG and IDH-wild-type HG exhibit distinct molecular signatures and have differential effects on tumor growth via regulation of ASPN-TGFβ1-GPM6A signaling.
Data from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

Abstract
The mechanistic basis for the metastasis of Ewing sarcomas remains poorly understood, as these tumors harbor few mutations beyond the chromosomal translocation that initiates the disease. Instead, the epigenome of Ewing sarcoma cells reflects the regulatory state of genes associated with the DNA-binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the EWSR1::FLI1/ERG's repression of transcription factor genes, concentrating on those that exhibit a broader range of expression in tumors than in Ewing sarcoma cell lines. Focusing on one of these target genes, ETS1, we detected EWSR1::FLI1 binding and an H3K27me3-repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1’s binding of promoter regions, substantially altering the transcriptome of Ewing sarcoma cells, including the upregulation of the gene encoding TENSIN3 (TNS3), a focal adhesion protein. Ewing sarcoma cell lines expressing ETS1 (CRISPRa) exhibited increased TNS3 expression and enhanced movement compared with control cells. Visualization of control Ewing sarcoma cells showed a distributed vinculin signal and a network-like organization of F-actin; in contrast, ETS1-activated Ewing sarcoma cells showed an accumulation of vinculin and F-actin toward the plasma membrane. Interestingly, the phenotype of ETS1-activated Ewing sarcoma cell lines depleted of TNS3 resembled the phenotype of the control cells. Critically, these findings have clinical relevance as TNS3 expression in Ewing sarcoma tumors positively correlates with that of ETS1.

Implications: ETS1’s transcriptional regulation of the gene encoding the focal adhesion protein TENSIN3 in Ewing sarcoma cells promotes cell movement, a critical step in the evolution of metastasis.
Data from Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway
Authors: Zhong Ying , Kang Hui , Ma Ziqing , Li Jiayu , Qin Zixi , Zhang Zixuan , Li Peiwen , Zhong Ying , Wang Lihui
Published: July 2024

Abstract
Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hEC) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma.
Implications:
These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.
Supplementary Table 1 from Nfe2l2/NRF2 Deletion Attenuates Tumorigenesis and Increases Bacterial Diversity in a Mouse Model of Lynch Syndrome
Authors: Haller Felix , Jimenez Kristine , Baumgartner Maximilian , Lang Michaela , Klotz Anton , Jambrich Manuela , Busslinger Georg , Müllauer Leonhard , Khare Vineeta , Gasche Christoph
Published: July 2024

Supplementary Table 1: Primer names and sequences.
Supplementary Figure 3 from Nfe2l2/NRF2 Deletion Attenuates Tumorigenesis and Increases Bacterial Diversity in a Mouse Model of Lynch Syndrome
Authors: Haller Felix , Jimenez Kristine , Baumgartner Maximilian , Lang Michaela , Klotz Anton , Jambrich Manuela , Busslinger Georg , Müllauer Leonhard , Khare Vineeta , Gasche Christoph
Published: July 2024

Supplementary Figure 3: At 1 month the microbiome of MSH2ΔIECNrf2null and MSH2ΔIEC mice was similar.
Supplementary Figure 6 from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Supplementary Figure 6. Expression analysis of selected exhaustion markers on different T cells on T cells in the tumor lesion used for TIL expansion.
Supplementary Table S4 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Primers used in assays
Supplementary Table S1 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Details of PNEN patients and healthy volunteers
Supplementary Fig. S8 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S8 THP-1 macrophages were incubated with 10 µg/ml PNEN cell-derived sEVs for 6 h, 12 h, 24 h and 48 h to show the kinetic.
Supplementary Figure 1 from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Supplementary Figure 1. Study Design of the BaseTIL trial. The BaseTIL trial was a phase I trial of tumor-infiltrating lymphocyte (TIL) therapy in combination with low dose interleukin-2 (IL2) and PD1 blockade with nivolumab for patients with metastatic melanoma.
Supplementary Fig. S6 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S6 The distribution of piRNA length (A), piRNA expression (B) and piRNA expression density (C) in each sample.
Supplementary Fig. S5 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

The RIP assay was conducted in THP-1 macrophages incubated with PNEN cell-derived sEVs
Supplementary Fig. S4 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S4 CD276 expression was detected in PNEN cells and PNEN cell-derived sEVs by western blot.
Supplementary Fig. S3 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S3 The association of CD3+ and CD8+ T cells with PNEN progression.
Supplementary Fig. S2 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S2 Representative mIHC images of CD3 in nontumor and tumor tissues (scale bar: 20 μm). The number of CD3+ T cells in tumor tissues was significantly higher than that in nontumor tissues. ***p < 0.001.
Supplementary Table S7 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Table S7
Supplementary Table S5 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Table S5
Supplementary Table S1 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Table S1
Supplementary Figure S9 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S9.
Supplementary Figure S8 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S8. TAA quantification on cell lines.
Supplementary Figure S7 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S7. MP0533 binding to MOLM-13 clones and T cells.
Supplementary Figure S5 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S5. TAA expression on AML and healthy donor samples.
Supplementary Figure S16 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S16. Binding to HUVEC cells.
Supplementary Figure S14 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S14. Killing of healthy cells.
Supplementary Figure S12 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S12.
Supplementary Figure 6 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S6. SIRT3 deficiency promotes TFH cell differentiation, GC responses in inhibiting the tumor growth.
Supplementary Figure 5 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S5. SIRT3 deficiency promotes TFH cell differentiation, GC responses in inhibiting the tumor growth.
Supplementary Table 2 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Table 2
Supplementary Figure 20 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig. S20. SIRT3 deficiency promotes TFH cell differentiation through mTOR-HIF1α coupled with the NAD+-dependent glucose metabolism pathway in human.
Supplementary Figure 2 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig. S2. SIRT3 expression is related to the TFH differentiation in cancer.
Supplementary Figure 19 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S19. SIRT3 deficiency promotes TFH differentiation through mTOR and NAD+ pathway.
Supplementary Figure 17 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S17. SIRT3 deficiency promotes TFH cell differentiation through mTOR-HIF1α coupled with the NAD+-dependent glucose metabolism pathway in mice.
Supplementary Figure 5 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Figure 5
Supplementary Figure 3 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Figure 3
Supplementary Figure 13 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig. S13. NAD+ levels are crucial for TFH cell differentiation induced by Sirt3∆CD4 in tumor.
Supplementary Figure 1 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Figure 1
Supplementary Figure 11 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig.S11. SIRT3 negatively affects efficient GC responses after immunization via antigen-specific mechanisms.
Figure 6 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

JHU083-induced glutamine antagonism causes extensive reprogramming of TILs. A, UMAP plot showing lymphocytic cell subsets identified from scRNA-seq analysis of CD45+ cells isolated from B6CaP tumors (JHU083-treated vs. control). B, UMAP density plots showing all NK and T cells. C, Dot plots of normalized expression of selected marker genes in T and NK cell subsets identified in A. D, Changes in proportions of NK cell subsets, stem cell–like CD8+ T cells, and CD4− Tregs from scRNA-seq (n = 3/group). E, Surface and intracellular expression of stem-like CD8+ T cells and Foxp3+ percentage population in B6CaP and MB49 tumors (n = 7/8 per group). F, Schematic workflow of T cell coculture with DON-pretreated human primary macrophages. G, CD8+ T cell proliferation measurement using autologous CD8+ T cells isolated from human PBMCs and cocultured with monocyte-derived macrophages pretreated with DON either during differentiation (days 0–9) or during polarization (days 5–9) phase. H, gMFI of TNF and IFNγ in cocultured autologous CD8+ T cells with DON pretreated monocyte-derived macrophages, and (I) Tumor volume measurement of MB49 and B6CaP tumors during the therapeutic window. Briefly, following the development of palpable tumors, tumor-bearing C57BL/6J mice were injected every third day with anti-PD1 alone or in combination with daily oral gavage of JHU083. The data are presented as mean values ± SEM. Statistical analyses were performed using either t test or a two-way ANOVA using Bonferroni’s multiple comparisons (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001). UMAP, uniform manifold approximation and projection for dimension reduction.
Figure 3 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

JHU083-induced glutamine antagonism promotes phagocytosis of tumor cells by TAMs and decreases angiogenesis in the TME. A, Tumor volume measurement of MB49 tumors in different treatment conditions. JHU083 treatment decreases tumor growth in MB49-RFP+ tumors relative to nontreated (n = 5 or 6/group) tumors. B, Representative flow cytometry plots of RFP+ MB49 tumor cells in TAMs in JHU083-treated vs. vehicle-treated tumors. C, Percentage of RFP+ cells within overall TAMs, CD206+ TAMs (M2-TAMs), and CD86+ MHCII+ TAMs (M1-TAMs) in MB49 tumors in control vs. JHU083-treated tumors. D, Percentage of RM1-RFP+ cells and corresponding mean fluorescence intensity (gMFI) of TAMs (n = 4/group) in control vs. JHU083-treated tumors. E, Schematic diagram showing the determination of the phagocytic activity of TAMs. Briefly, DON-treated, PBMC-derived macrophages were cocultured with CFSE-labeled PC3 cells, and phagocytic activity was determined using flow cytometry. F, Representative photomicrographs showing increased phagocytosis in DON-treated and PKH26-labeled macrophages (PKH26 MAC) cocultured with CFSE-labeled PC3 (CFSE PC3) by immunofluorescence microscopy and quantification using flow cytometry. G, Violin plots of phagocytosis UCell scores on TAM_1, TAM_2, Inflam_TAM, and Prolif_TAM (Wilcoxon rank-sum test) identified in scRNA-seq analysis of CD45+ cells from B6CaP tumors. H, Violin plot for Myo1e expression in all TAMs in B6CaP-derived TAMs identified in scRNA-seq analysis of CD45+ cells from B6CaP tumors. I, IHC-based quantification of CD31+ area intensity in B6CaP tumors (n = 3/group), and (J) IHC quantification of CD31 intensity in MB49 tumors. Statistical analyses were performed using t test or two-way ANOVA using Bonferroni’s multiple comparisons. Violin plots from scRNA-seq studies are analyzed using the Wilcoxon rank-sum test. (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001).