bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure from IFNα Potentiates Anti–PD-1 Efficacy by Remodeling Glucose Metabolism in the Hepatocellular Carcinoma Microenvironment
Authors: Hu Bo , Yu Mincheng , Ma Xiaolu , Sun Jialei , Liu Chenglong , Wang Chunyan , Wu Suiyi , Fu Peiyao , Yang Zhen , He Yungang , Zhu Yuanyuan , Huang Cheng , Yang Xinrong , Shi Yinghong , Qiu Shuangjian , Sun Huichuan , Zhu Andrew X. , Zhou Jian , Xu Yang , Zhu Di , Fan Jia
Published: April 2023

Supplementary Figure from IFNα Potentiates Anti–PD-1 Efficacy by Remodeling Glucose Metabolism in the Hepatocellular Carcinoma Microenvironment
Table S3 from Maelstrom Directs Myeloid-Derived Suppressor Cells to Promote Esophageal Squamous Cell Carcinoma Progression via Activation of the Akt1/RelA/IL8 Signaling Pathway
Authors: Li Pupu , Chen Xinfeng , Qin Guohui , Yue Dongli , Zhang Zhen , Ping Yu , Wang Dan , Zhao Xuan , Song Mengjia , Zhao Qitai , Li Jieyao , Liu Shasha , Wang Dong , Zhang Chaoqi , Lian Jingyao , Cao Ling , Li Feng , Huang Lan , Wang Liping , Yang Li , Huang Jianmin , Li Hong , Zhang Bin , Zhang Yi
Published: April 2023

Correlation analysis between the expression of MAEL and clinicopathological parameters in ESCC patients.
Supplementary Methods from Novel Mechanism of Tumor Suppression by Polarity Gene Discs Large 1 (DLG1) Revealed in a Murine Model of Pediatric B-ALL
Authors: Sandoval Gabriel J. , Graham Daniel B. , Gmyrek Grzegorz B. , Akilesh Holly M. , Fujikawa Keiko , Sammut Benedicte , Bhattacharya Deepta , Srivatsan Shuba , Kim Alfred , Shaw Andrey S. , Yang-Iott Katherine , Bassing Craig H. , Duncavage Eric , Xavier Ramnik J. , Swat Wojciech
Published: April 2023

PDF file - 81K
Supplementary Methods, Figure Legend from Antigen-Specific Bacterial Vaccine Combined with Anti-PD-L1 Rescues Dysfunctional Endogenous T Cells to Reject Long-Established Cancer
Authors: Binder David C. , Engels Boris , Arina Ainhoa , Yu Ping , Slauch James M. , Fu Yang-Xin , Karrison Theodore , Burnette Byron , Idel Christian , Zhao Ming , Hoffman Robert M. , Munn David H. , Rowley Donald A. , Schreiber Hans
Published: April 2023

PDF file - 122K
Supplementary Figure 2 from Inhibition of Soluble Tumor Necrosis Factor Prevents Chemically Induced Carcinogenesis in Mice
Authors: Sobo-Vujanovic Andrea , Vujanovic Lazar , DeLeo Albert B. , Concha-Benavente Fernando , Ferris Robert L. , Lin Yan , Vujanovic Nikola L.
Published: April 2023

MCA doesn't affect while sTNF exclusion decreases frequency of macrophages. Experimental groups were set up as described in Fig. 3 legend. Splenocytes were simultaneously stained with anti-CD45R-FITC and anti-F4/80-PE antibodies, and examined by two-color flow cytometry. (A) Gating strategies: Gate 1, single cells; Gate 2, mononuclear cells; and Gate 3, CD45+ and F4/80+ mononuclear cells showing all individual data. (B) Bar-graph presents CD45-F4/80+ splenic macrophages showing individual and mean (2-3 replicates) + SD percentages of positive cells.
Supplementary Figure 1 from Inhibition of Soluble Tumor Necrosis Factor Prevents Chemically Induced Carcinogenesis in Mice
Authors: Sobo-Vujanovic Andrea , Vujanovic Lazar , DeLeo Albert B. , Concha-Benavente Fernando , Ferris Robert L. , Lin Yan , Vujanovic Nikola L.
Published: April 2023

Gating strategy for three-color flow cytometry analysis of splenic MDSCs. Splenocytes were simultaneously stained with anti-CD11b-FITC, anti-Gr1-PE and anti-Ly6C-APC antibodies or the corresponding isotype control antibodies and analyzed by flow cytometry as follows. Gate 1: single cells were gated and cell aggregates were excluded. Gate 2: using side-scatter (SSC) and forward-scatter (FSC), granular and non-granular (mononuclear) cells were gated. Gate 3: CD11b+ granular (A) and mononuclear (B) cells were gated. Gate 4: Gr1 and Ly6 expression on CD11b+ granular (A) and mononuclear (B) cells was examined.
Supplementary Tables 1 through 4 from Angiopoietin-2 as a Biomarker and Target for Immune Checkpoint Therapy
Authors: Wu Xinqi , Giobbie-Hurder Anita , Liao Xiaoyun , Connelly Courtney , Connolly Erin M. , Li Jingjing , Manos Michael P. , Lawrence Donald , McDermott David , Severgnini Mariano , Zhou Jun , Gjini Evisa , Lako Ana , Lipschitz Mikel , Pak Christine J. , Abdelrahman Sara , Rodig Scott , Hodi F. Stephen
Published: April 2023

Table S1. Patient characteristics. Table S2. Patient characteristics by pre-treatment serum ANGPT2 levels. Table S3. Serum ANGPT2 fold-changes by immune checkpoint therapy. Table S4. ANGPT2, CD68 and CD163 staining of melanoma tissues.
Supplementary Figure 8 from STING Ligand c-di-GMP Improves Cancer Vaccination against Metastatic Breast Cancer
Authors: Chandra Dinesh , Quispe-Tintaya Wilber , Jahangir Arthee , Asafu-Adjei Denise , Ramos Ilyssa , Sintim Herman O. , Zhou Jie , Hayakawa Yoshihiro , Karaolis David K.R. , Gravekamp Claudia
Published: April 2023

PDF file - 98K, Figure S8: The effect of c-di-GMP on CD4 and CD8 T cell populations in the lymph nodes of 4T1 tumor-bearing mice.
Supplementary Figure 10 from STING Ligand c-di-GMP Improves Cancer Vaccination against Metastatic Breast Cancer
Authors: Chandra Dinesh , Quispe-Tintaya Wilber , Jahangir Arthee , Asafu-Adjei Denise , Ramos Ilyssa , Sintim Herman O. , Zhou Jie , Hayakawa Yoshihiro , Karaolis David K.R. , Gravekamp Claudia
Published: April 2023

PDF file - 164K, Figure S10: Gating of MDSC in blood of 4T1 tumor-bearing mice.
Supplementary Tables 1 and 2 and Supplementary Figures 1 and 2 from Antitumor Efficacy of Anti-GD2 IgG1 Is Enhanced by Fc Glyco-Engineering
Authors: Xu Hong , Guo Hongfen , Cheung Irene Y. , Cheung Nai-Kong V.
Published: April 2023

Supplemental Table S1: Affinities relative to hu3F8-IgG1. Supplemental Table S2: Affinities to both human and mouse FcR(n). Supplemental Figure S1: Kinetic analysis of in vitro binding of antibodies to CD16A(158V) by SPR. Supplemental Figure S2: Blood clearance of the antibodies in nude mice.
Supplemental Figure S3 from Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade
Authors: Kelleher Raymond J. , Balu-Iyer Sathy , Loyall Jenni , Sacca Anthony J. , Shenoy Gautam N. , Peng Peng , Iyer Vandana , Fathallah Anas M. , Berenson Charles S. , Wallace Paul K. , Tario Joseph , Odunsi Kunle , Bankert Richard B.
Published: April 2023

Fig S3. Sorting of lymphocytes into CD4+ and CD8+ subsets.
Supplementary Figure 1 from Using Quantitative Seroproteomics to Identify Antibody Biomarkers in Pancreatic Cancer
Authors: Jhaveri Darshil T. , Kim Min-Sik , Thompson Elizabeth D. , Huang Lanqing , Sharma Rajni , Klein Alison P. , Zheng Lei , Le Dung T. , Laheru Daniel A. , Pandey Akhilesh , Jaffee Elizabeth M. , Anders Robert A.
Published: April 2023

Venn diagram showing overlap of proteins identified in 3 patients after the SASI screen.
Supplemental Methods from Identification of Anti-CA125 Antibody Responses in Ovarian Cancer Patients by a Novel Deep Sequence–Coupled Biopanning Platform
Authors: Frietze Kathryn M. , Roden Richard B.S. , Lee Ji-Hyun , Shi Yang , Peabody David S. , Chackerian Bryce
Published: April 2023

Supplemental Methods
Supplementary Figure Legends from Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model
Authors: Reardon David A. , Gokhale Prafulla C. , Klein Sarah R. , Ligon Keith L. , Rodig Scott J. , Ramkissoon Shakti H. , Jones Kristen L. , Conway Amy Saur , Liao Xiaoyun , Zhou Jun , Wen Patrick Y. , Van Den Abbeele Annick D. , Hodi F. Stephen , Qin Lei , Kohl Nancy E. , Sharpe Arlene H. , Dranoff Glenn , Freeman Gordon J.
Published: April 2023

Supplementary Figure Legends
Supplementary Figure 4 from Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma
Authors: Hodi F. Stephen , Lawrence Donald , Lezcano Cecilia , Wu Xinqi , Zhou Jun , Sasada Tetsuro , Zeng Wanyong , Giobbie-Hurder Anita , Atkins Michael B. , Ibrahim Nageatte , Friedlander Philip , Flaherty Keith T. , Murphy George F. , Rodig Scott , Velazquez Elsa F. , Mihm Martin C. , Russell Sara , DiPiro Pamela J. , Yap Jeffrey T. , Ramaiya Nikhil , Van den Abbeele Annick D. , Gargano Maria , McDermott David
Published: April 2023

PDF file - 125K, Individual response of CCR7+CD45RO+ and CCD7-CD45RO+ of CD4+ and CD8+ T cells in melanoma patients treated with ipilimumab (3mg/kg), ipilimumab (3mg/kg) plus bevacizumab, or ipilimumab (10mg/kg) plus bevacizumab.
Supplementary Figure 1 from Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma
Authors: Hodi F. Stephen , Lawrence Donald , Lezcano Cecilia , Wu Xinqi , Zhou Jun , Sasada Tetsuro , Zeng Wanyong , Giobbie-Hurder Anita , Atkins Michael B. , Ibrahim Nageatte , Friedlander Philip , Flaherty Keith T. , Murphy George F. , Rodig Scott , Velazquez Elsa F. , Mihm Martin C. , Russell Sara , DiPiro Pamela J. , Yap Jeffrey T. , Ramaiya Nikhil , Van den Abbeele Annick D. , Gargano Maria , McDermott David
Published: April 2023

PDF file - 76K, CONSORT Diagram.
Supplementary Materials and Methods from Type I Cytokines Synergize with Oncogene Inhibition to Induce Tumor Growth Arrest
Authors: Acquavella Nicolas , Clever David , Yu Zhiya , Roelke-Parker Melody , Palmer Douglas C. , Xi Liqiang , Pflicke Holger , Ji Yun , Gros Alena , Hanada Ken-ichi , Goldlust Ian S. , Mehta Gautam U. , Klebanoff Christopher A. , Crompton Joseph G. , Sukumar Madhusudhanan , Morrow James J. , Franco Zulmarie , Gattinoni Luca , Liu Hui , Wang Ena , Marincola Francesco , Stroncek David F. , Lee Chyi-Chia R. , Raffeld Mark , Bosenberg Marcus W. , Roychoudhuri Rahul , Restifo Nicholas P.
Published: April 2023

Supplementary Materials and Methods
Supplementary Figure S2 from The Different T-cell Receptor Repertoires in Breast Cancer Tumors, Draining Lymph Nodes, and Adjacent Tissues
Authors: Wang Ting , Wang Changxi , Wu Jinghua , He Chenyang , Zhang Wei , Liu Jiayun , Zhang Ruifang , Lv Yonggang , Li Yongping , Zeng Xiaojing , Cao Hongzhi , Zhang Xiuqing , Xu Xun , Huang Chen , Wang Ling , Liu Xiao
Published: April 2023

TRB repertoire diversity of lymph node, non-tumor and tumor tissue.
supplemental figure 2 from Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab
Authors: Weber Jeffrey , Gibney Geoffrey , Kudchadkar Ragini , Yu Bin , Cheng Pingyan , Martinez Alberto J. , Kroeger Jodie , Richards Allison , McCormick Lori , Moberg Valerie , Cronin Heather , Zhao Xiuhua , Schell Michael , Chen Yian Ann
Published: April 2023

Suppression of T-cell proliferation by MDSC
Supplementary Table 1 from PD-1 Blockade Expands Intratumoral Memory T Cells
Authors: Ribas Antoni , Shin Daniel Sanghoon , Zaretsky Jesse , Frederiksen Juliet , Cornish Andrew , Avramis Earl , Seja Elizabeth , Kivork Christine , Siebert Janet , Kaplan-Lefko Paula , Wang Xiaoyan , Chmielowski Bartosz , Glaspy John A. , Tumeh Paul C. , Chodon Thinle , Pe'er Dana , Comin-Anduix Begoña
Published: April 2023

Fluorochromes used on this study
Supplementary Table S2 from Neoantigen Load, Antigen Presentation Machinery, and Immune Signatures Determine Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Matsushita Hirokazu , Sato Yusuke , Karasaki Takahiro , Nakagawa Tohru , Kume Haruki , Ogawa Seishi , Homma Yukio , Kakimi Kazuhiro
Published: April 2023

HLA-restricted neoepitopes and expression of HLA/B2M
Supplementary Figure S1 from Neoantigen Load, Antigen Presentation Machinery, and Immune Signatures Determine Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Matsushita Hirokazu , Sato Yusuke , Karasaki Takahiro , Nakagawa Tohru , Kume Haruki , Ogawa Seishi , Homma Yukio , Kakimi Kazuhiro
Published: April 2023

Kaplan-Meier survival curves in 97 ccRCC patients stratified according to the sex, age, Stage and Fuhrman grade
Supplementary Figure Legends from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Authors: Shen Li , Sundstedt Anette , Ciesielski Michael , Miles Kiersten Marie , Celander Mona , Adelaiye Remi , Orillion Ashley , Ciamporcero Eric , Ramakrishnan Swathi , Ellis Leigh , Fenstermaker Robert , Abrams Scott I. , Eriksson Helena , Leanderson Tomas , Olsson Anders , Pili Roberto
Published: April 2023

Supplementary Figure Legends from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Supplementary Figure 6 from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Authors: Shen Li , Sundstedt Anette , Ciesielski Michael , Miles Kiersten Marie , Celander Mona , Adelaiye Remi , Orillion Ashley , Ciamporcero Eric , Ramakrishnan Swathi , Ellis Leigh , Fenstermaker Robert , Abrams Scott I. , Eriksson Helena , Leanderson Tomas , Olsson Anders , Pili Roberto
Published: April 2023

Supplementary Figure 6. The effect of tasquinimod on nitric oxide synthase activity in infiltrating myeloid cells.
Supplementary Figure 3 from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Authors: Shen Li , Sundstedt Anette , Ciesielski Michael , Miles Kiersten Marie , Celander Mona , Adelaiye Remi , Orillion Ashley , Ciamporcero Eric , Ramakrishnan Swathi , Ellis Leigh , Fenstermaker Robert , Abrams Scott I. , Eriksson Helena , Leanderson Tomas , Olsson Anders , Pili Roberto
Published: April 2023

Supplementary Figure 3. CD11b+ in tumor and MDSC subpopulations in spleen from B16-h5T4 tumor bearing C57/Bl6 mice.
Supplementary Figure 1 from Tasquinimod Modulates Suppressive Myeloid Cells and Enhances Cancer Immunotherapies in Murine Models
Authors: Shen Li , Sundstedt Anette , Ciesielski Michael , Miles Kiersten Marie , Celander Mona , Adelaiye Remi , Orillion Ashley , Ciamporcero Eric , Ramakrishnan Swathi , Ellis Leigh , Fenstermaker Robert , Abrams Scott I. , Eriksson Helena , Leanderson Tomas , Olsson Anders , Pili Roberto
Published: April 2023

Supplementary Figure 1. Survivin peptide vaccine, SurVaxM, induced antigen-specific CD8 effector cells in the tumor bearing animals.
Supplementary Figure S1 from Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab
Authors: Kwek Serena S. , Lewis Jera , Zhang Li , Weinberg Vivian , Greaney Samantha K. , Harzstark Andrea L. , Lin Amy M. , Ryan Charles J. , Small Eric J. , Fong Lawrence
Published: April 2023

Supplementary Figure S1. Patient baseline characteristics.
Supplementary Figure 2 from Tumor Subtype-Specific Cancer–Testis Antigens as Potential Biomarkers and Immunotherapeutic Targets for Cancers
Authors: Yao Jun , Caballero Otavia L. , Yung W.K. Alfred , Weinstein John N. , Riggins Gregory J. , Strausberg Robert L. , Zhao Qi
Published: April 2023

PDF file - 753K, Gene expression heatmap of top prognostic genes in KIRC.
Supplementary Table 6 from Somatic Mutations and Immune Alternation in Rectal Cancer Following Neoadjuvant Chemoradiotherapy
Authors: Ji Dengbo , Yi Haizhao , Zhang Dakui , Zhan Tiancheng , Li Zhaowei , Li Ming , Jia Jinying , Qiao Meng , Xia Jinhong , Zhai Zhiwei , Song Can , Gu Jin
Published: April 2023

Supplementary Table 6. HLA reference set
Supplementary data from Circulating Tumor Microparticles Promote Lung Metastasis by Reprogramming Inflammatory and Mechanical Niches via a Macrophage-Dependent Pathway
Authors: Zhang Huafeng , Yu Yuandong , Zhou Li , Ma Jingwei , Tang Ke , Xu Pingwei , Ji Tiantian , Liang Xiaoyu , Lv Jiadi , Dong Wenqian , Zhang Tianzhen , Chen Degao , Xie Jing , Liu Yuying , Huang Bo
Published: April 2023

Supplementary Figure S1. Size distribution of T-MPs isolated from hypoxic or normoxic tumor cells. Supplementary Figure S2. Analysis of lung metastasis and overall survival after tail vein injection of 4T1 breast cancer cells in mice pretreated with 4T1-MPï¼ŒS-MP or PBS. Supplementary Figure S3. Confocal microscopic analysis of PKH26-MPs in lung. Supplementary Figure S4. Analysis of lung endothelial permeability. Supplementary Figure S5. The proportion of T cells, B cells and NK cells in the lungs were analyzed by flow cytometry after treatment of with 4T1-MPï¼ŒS-MP or PBS. Supplementary Figure S6. CCL2 was mainly produced by lung macrophages that had taken up T-MPs. Figure S7. DNA fragments in hypoxic tumor cell-MPs contribute to macrophages upregulating CCL2 expression via the cGAS/STING/STAT6 pathway. Supplementary Figure S8. CCL2-attracted monocytes transit to macrophages. Supplementary Figure S9. F4/80+CD11b+Ly6C- macrophages effectively inhibited OVA257-264 peptide-stimulated OT-1 T cell proliferation in vitro and in vivo. Supplementary Figure S10. T-MP-induced VEGF production by macrophages contributes fibrin deposition in the lungs.
Supplementary Data from IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype
Authors: Alizadeh Darya , Wong Robyn A. , Yang Xin , Wang Dongrui , Pecoraro Joseph R. , Kuo Cheng-Fu , Aguilar Brenda , Qi Yue , Ann David K. , Starr Renate , Urak Ryan , Wang Xiuli , Forman Stephen J. , Brown Christine E.
Published: April 2023

Supp Fig 1 Compares IL2 alone to manufacturing platform. Supp Fig 2 Product post-enrichment. Supp Fig 3 Additional characterization of IL2 and IL15 cultured CAR-T cells. Supp Fig 4 Heat map comparing CD4 gene expression differences in IL2 and IL15 cultured CAR-T cells. Supp Fig 5 Additional phenotypic and functional characterizations Supp Fig 6 Comparison of PBMC-derived to CD62L-derived CAR-T cells in IL2 and IL15 culture condition. Supp Fig 7 Phenotypic and functional assessment of 4-1BB-CAR-T cultured in IL15 and IL2. Supp Fig 8 Comparison of expansion, �R+ and CD4/CD8 populations in CAR-T cells cultured in difference cytokine conditions. Supp Fig 9 Comparison of low-dose IL2 with IL15 alone and standard manufacturing platform IL2. Supp Table 1 Primer list
Supplementary Data from Immunopathologic Stratification of Colorectal Cancer for Checkpoint Blockade Immunotherapy
Authors: Llosa Nicolas J. , Luber Brandon , Siegel Nicholas , Awan Anas H. , Oke Teniola , Zhu Qingfeng , Bartlett Bjarne R. , Aulakh Laveet K. , Thompson Elizabeth D. , Jaffee Elizabeth M. , Durham Jennifer N. , Sears Cynthia L. , Le Dung T. , Diaz Luis A. , Pardoll Drew M. , Wang Hao , Housseau Franck , Anders Robert A.
Published: April 2023

Supplementary figures 1-6 and tables 1-3
Supplementary Figures and Tables from Lactate-Modulated Immunosuppression of Myeloid-Derived Suppressor Cells Contributes to the Radioresistance of Pancreatic Cancer
Authors: Yang Xuguang , Lu Yun , Hang Junjie , Zhang Junfeng , Zhang Tiening , Huo Yanmiao , Liu Jun , Lai Songtao , Luo Dawei , Wang Liwei , Hua Rong , Lin Yuli
Published: April 2023

Supplementary Figures S1-S8 and Tables S1-S3
Supplementary Table S5 from Spliced Peptides and Cytokine-Driven Changes in the Immunopeptidome of Melanoma
Authors: Faridi Pouya , Woods Katherine , Ostrouska Simone , Deceneux Cyril , Aranha Ritchlynn , Duscharla Divya , Wong Stephen Q. , Chen Weisan , Ramarathinam Sri H. , Lim Kam Sian Terry C.C. , Croft Nathan P. , Li Chen , Ayala Rochelle , Cebon Jonathan S. , Purcell Anthony W. , Schittenhelm Ralf B. , Behren Andreas
Published: April 2023

Table S5
Figure S6 from Virus-Like Particle–Drug Conjugates Induce Protective, Long-lasting Adaptive Antitumor Immunity in the Absence of Specifically Targeted Tumor Antigens
Authors: Kines Rhonda C. , Thompson Cynthia D. , Spring Sean , Li Zhenyu , de los Pinos Elisabet , Monks Stephen , Schiller John T.
Published: April 2023

Examples of AU-011 efficacy in other tumor survival models.
Figure S1 from Virus-Like Particle–Drug Conjugates Induce Protective, Long-lasting Adaptive Antitumor Immunity in the Absence of Specifically Targeted Tumor Antigens
Authors: Kines Rhonda C. , Thompson Cynthia D. , Spring Sean , Li Zhenyu , de los Pinos Elisabet , Monks Stephen , Schiller John T.
Published: April 2023

In vivo efficacy of AU-011.
Supplementary Data from Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses
Authors: Greaney Samantha K. , Algazi Alain P. , Tsai Katy K. , Takamura Kathryn T. , Chen Lawrence , Twitty Christopher G. , Zhang Li , Paciorek Alan , Pierce Robert H. , Le Mai H. , Daud Adil I. , Fong Lawrence
Published: April 2023

Supplementary Data
Figure S6 from Verteporfin Inhibits PD-L1 through Autophagy and the STAT1–IRF1–TRIM28 Signaling Axis, Exerting Antitumor Efficacy
Authors: Liang Jiyong , Wang Lulu , Wang Chao , Shen Jianfeng , Su Bojin , Marisetty Anantha L. , Fang Dexing , Kassab Cynthia , Jeong Kang Jin , Zhao Wei , Lu Yiling , Jain Abhinav K. , Zhou Zhicheng , Liang Han , Sun Shao-Cong , Lu Changming , Xu Zhi-Xiang , Yu Qinghua , Shao Shan , Chen XiaoHua , Gao Meng , Claret Francois X. , Ding Zhiyong , Chen Jian , Chen Pingsheng , Barton Michelle C. , Peng Guang , Mills Gordon B. , Heimberger Amy B.
Published: April 2023

Supplemental FigureS6
Figure S3 from Verteporfin Inhibits PD-L1 through Autophagy and the STAT1–IRF1–TRIM28 Signaling Axis, Exerting Antitumor Efficacy
Authors: Liang Jiyong , Wang Lulu , Wang Chao , Shen Jianfeng , Su Bojin , Marisetty Anantha L. , Fang Dexing , Kassab Cynthia , Jeong Kang Jin , Zhao Wei , Lu Yiling , Jain Abhinav K. , Zhou Zhicheng , Liang Han , Sun Shao-Cong , Lu Changming , Xu Zhi-Xiang , Yu Qinghua , Shao Shan , Chen XiaoHua , Gao Meng , Claret Francois X. , Ding Zhiyong , Chen Jian , Chen Pingsheng , Barton Michelle C. , Peng Guang , Mills Gordon B. , Heimberger Amy B.
Published: April 2023

Supplemental Figure S3
Supplementary Figure Legends, Tables and Methods from The Combined Effect of FGFR Inhibition and PD-1 Blockade Promotes Tumor-Intrinsic Induction of Antitumor Immunity
Authors: Palakurthi Sangeetha , Kuraguchi Mari , Zacharek Sima J. , Zudaire Enrique , Huang Wei , Bonal Dennis M. , Liu Jeffrey , Dhaneshwar Abha , DePeaux Kristin , Gowaski Martha R. , Bailey Dyane , Regan Samuel N. , Ivanova Elena , Ferrante Catherine , English Jessie M. , Khosla Aditya , Beck Andrew H. , Rytlewski Julie A. , Sanders Catherine , Laquerre Sylvie , Bittinger Mark A. , Kirschmeier Paul T. , Packman Kathryn , Janne Pasi A. , Moy Christopher , Wong Kwok-Kin , Verona Raluca I. , Lorenzi Matthew V.
Published: April 2023

Supplemental figure legends 1-8, Supplementary tables 1-5, and Supplementary methods
Figure S5 from Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development
Authors: Gui Xun , Deng Mi , Song Hao , Chen Yuanzhi , Xie Jingjing , Li Zunling , He Licai , Huang Fangfang , Xu Yixiang , Anami Yasuaki , Yu Hai , Yu Chenyi , Li Leike , Yuan Zihao , Xu Xiaoying , Wang Qihui , Chai Yan , Huang Tao , Shi Yi , Tsuchikama Kyoji , Liao X. Charlene , Xia Ningshao , Gao George F. , Zhang Ningyan , Zhang Cheng Cheng , An Zhiqiang
Published: April 2023

h128-3 blocks AML THP-1 cells tissue infiltration in a time-dependent manner.
Supplementary Figure 5 from Long-term Sculpting of the B-cell Repertoire following Cancer Immunotherapy in Patients Treated with Sipuleucel-T
Authors: Zhang Li , Kandadi Harini , Yang Hai , Cham Jason , He Tao , Oh David Y. , Sheikh Nadeem A. , Fong Lawrence
Published: April 2023

Supplementary Fig. 5: Sensitivity analysis of social network analysis of the representative sipuleucel-T treated patient. (A) Density plot of the clone frequency for all clones of the treated patient (red) and density plot of the clone frequency for subsampled clones of the treated patient (green). Subsampling was done by weighted clone frequency. (B) Social network (V04 family gene) of the all clones of the treated patient. (C) Social network (V04 family gene) of the all clones of the naïve patient. (D) Social network (V04 family gene) of the subsampled clones of the treated patient. Subsampling was done by weighted clone frequency. For each patient, social network analysis was first performed using R packages: Ape (24) and igraph (25). A convergent group was defined as the cluster that included the clones with the distance less than or equal to 1 (allowing maximum of 1 basepair mutation among clone sequences sharing the same V-gene, J-gene and CDR3 length). For all social network figures, each node represents a single clone colored by its first presenting time point, and the node size was attributed based on the corresponding abundance. The nodes connected by lines were within the same convergent group.
Supplementary Figure 2 from Long-term Sculpting of the B-cell Repertoire following Cancer Immunotherapy in Patients Treated with Sipuleucel-T
Authors: Zhang Li , Kandadi Harini , Yang Hai , Cham Jason , He Tao , Oh David Y. , Sheikh Nadeem A. , Fong Lawrence
Published: April 2023

Supplementary Fig. 2A: Changes in rank of the top 100 BCR clones at week 2 for a representative naïve patient are shown. The top 100 clonotypes at week 2 were identified based on their abundances at week 2. The rank of those clones at other timepoints were also obtained, and plotted across all 6 time points. Supplementary Fig. 2B: Pairwise Morisita's distance for both treated and naïve. Morisita's distance of 0 and 1 means maximally and minimally dissimilar of the repertoires from two different time points of the same patient, respectively (27). Each panel illustrates the Morisita's distance of two time points. Within each panel left and right boxplots represent sipuleucel-T treated patients and sipuleucel-T naive patients, respectively. The asterisk shows significant higher in treated vs naïve (Wilcoxon sum rank test p<0.05).
Figure S2 from Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development
Authors: Gui Xun , Deng Mi , Song Hao , Chen Yuanzhi , Xie Jingjing , Li Zunling , He Licai , Huang Fangfang , Xu Yixiang , Anami Yasuaki , Yu Hai , Yu Chenyi , Li Leike , Yuan Zihao , Xu Xiaoying , Wang Qihui , Chai Yan , Huang Tao , Shi Yi , Tsuchikama Kyoji , Liao X. Charlene , Xia Ningshao , Gao George F. , Zhang Ningyan , Zhang Cheng Cheng , An Zhiqiang
Published: April 2023

Schematic diagram showing the construction of LILRB4 fragments fused with Fc of human IgG1.
Supplementary Figure 1 from DGKA Mediates Resistance to PD-1 Blockade
Authors: Fu Lingyi , Li Sen , Xiao WeiWei , Yu Kuai , Li Shuo , Yuan Sujing , Shen Jianfei , Dong Xingjun , Fang Ziqian , Zhang Jianeng , Chen Siyu , Li Wende , You Hua , Xia Xiaojun , Kang Tiebang , Tan Jing , Chen Gong , Yang An-Kui , Gao YuanHong , Zhou Penghui
Published: April 2023

Supplementary Figure 1
Supplementary Table 1 from Targeting Triple-Negative Breast Cancer with Combination Therapy of EGFR CAR T Cells and CDK7 Inhibition
Authors: Xia Lin , Zheng Zaozao , Liu Jun-yi , Chen Yu-jie , Ding Jiancheng , Hu Guo-sheng , Hu Ya-hong , Liu Suling , Luo Wen-xin , Xia Ning-shao , Liu Wen
Published: April 2023

Supplementary Table 1
Supplementary Figure 7 from The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8+ T-cell Responses and Promotes Tumor Growth
Authors: Chen Siqi , Akdemir Imran , Fan Jie , Linden Joel , Zhang Bin , Cekic Caglar
Published: April 2023

Supplementary Figure 7
Supplementary Figure 5 from The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8+ T-cell Responses and Promotes Tumor Growth
Authors: Chen Siqi , Akdemir Imran , Fan Jie , Linden Joel , Zhang Bin , Cekic Caglar
Published: April 2023

Supplementary Figure 5
Supplementary Figure 1 from The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8+ T-cell Responses and Promotes Tumor Growth
Authors: Chen Siqi , Akdemir Imran , Fan Jie , Linden Joel , Zhang Bin , Cekic Caglar
Published: April 2023

Supplementary Figure 1
Supplementary Data from Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers
Authors: Colbert Lauren E. , El Molly B. , Lynn Erica J. , Bronk Julianna , Karpinets Tatiana V. , Wu Xiaogang , Chapman Bhavana V. , Sims Travis T. , Lin Daniel , Kouzy Ramez , Sammouri Julie , Biegert Greyson , Delgado Medrano Andrea Y. , Olvera Adilene , Sastry K. Jagannadha , Eifel Patricia J. , Jhingran Anuja , Lin Lilie , Ramondetta Lois M. , Futreal Andrew P. , Jazaeri Amir A. , Schmeler Kathleen M. , Yue Jingyan , Mitra Aparna , Yoshida-Court Kyoko , Wargo Jennifer A. , Solley Travis N. , Hegde Venkatesh , Nookala Sita S. , Yanamandra Ananta V. , Dorta-Estremera Stephanie , Mathew Geena , Kavukuntla Rohit , Papso Cassidy , Ahmed-Kaddar Mustapha , Kim Minsoo , Zhang Jianhua , Reuben Alexandre , Holliday Emma B. , Minsky Bruce D. , Koong Albert C. , Koay Eugene J. , Das Prajnan , Taniguchi Cullen M. , Klopp Ann
Published: April 2023

Supplementary Data
Supplemental Figures and Legends
Supplemental Tables from Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers
Authors: Colbert Lauren E. , El Molly B. , Lynn Erica J. , Bronk Julianna , Karpinets Tatiana V. , Wu Xiaogang , Chapman Bhavana V. , Sims Travis T. , Lin Daniel , Kouzy Ramez , Sammouri Julie , Biegert Greyson , Delgado Medrano Andrea Y. , Olvera Adilene , Sastry K. Jagannadha , Eifel Patricia J. , Jhingran Anuja , Lin Lilie , Ramondetta Lois M. , Futreal Andrew P. , Jazaeri Amir A. , Schmeler Kathleen M. , Yue Jingyan , Mitra Aparna , Yoshida-Court Kyoko , Wargo Jennifer A. , Solley Travis N. , Hegde Venkatesh , Nookala Sita S. , Yanamandra Ananta V. , Dorta-Estremera Stephanie , Mathew Geena , Kavukuntla Rohit , Papso Cassidy , Ahmed-Kaddar Mustapha , Kim Minsoo , Zhang Jianhua , Reuben Alexandre , Holliday Emma B. , Minsky Bruce D. , Koong Albert C. , Koay Eugene J. , Das Prajnan , Taniguchi Cullen M. , Klopp Ann
Published: April 2023

Supplemental Tables
Tables S1-S13
Supplementary Figures from C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models
Authors: Nandagopal Saravanan , Li Caiyun G. , Xu Yu , Sodji Quaovi H. , Graves Edward E. , Giaccia Amato J.
Published: April 2023

Supplementary figures and legends S1-S8
Supplementary Tables from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation
Authors: Xie Stephanie Z. , Kaufmann Kerstin B. , Wang Weijia , Chan-Seng-Yue Michelle , Gan Olga I. , Laurenti Elisa , Garcia-Prat Laura , Takayanagi Shin-ichiro , Ng Stanley W.K. , Xu ChangJiang , Zeng Andy G.X. , Jin Liqing , McLeod Jessica , Wagenblast Elvin , Mitchell Amanda , Kennedy James A. , Liu Qiang , Boutzen Héléna , Kleinau Melissa , Jargstorf Joseph , Holmes Gareth , Zhang Yang , Voisin Veronique , Bader Gary D. , Wang Jean C.Y. , Hannun Yusuf A. , Luberto Chiara , Schroeder Timm , Minden Mark D. , Dick John E.
Published: April 2023

Supplementary tables 1 to 14
Figure S5 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander
Published: April 2023

Non-uniform dynamics of single CpGs among CLL progression
Figure S4 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander
Published: April 2023

Treatment with venetoclax does not result in a reset of the epigenome
Tables S1-S5 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy
Authors: Jeha Sima , Choi John , Roberts Kathryn G. , Pei Deqing , Coustan-Smith Elaine , Inaba Hiroto , Rubnitz Jeffrey E. , Ribeiro Raul C. , Gruber Tanja A. , Raimondi Susana C. , Karol Seth E. , Qu Chunxu , Brady Samuel W. , Gu Zhaohui , Yang Jun J. , Cheng Cheng , Downing James R. , Evans Williams E. , Relling Mary V. , Campana Dario , Mullighan Charles G. , Pui Ching-Hon
Published: April 2023

Supplementary Table S1-S5
Table S6 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy
Authors: Jeha Sima , Choi John , Roberts Kathryn G. , Pei Deqing , Coustan-Smith Elaine , Inaba Hiroto , Rubnitz Jeffrey E. , Ribeiro Raul C. , Gruber Tanja A. , Raimondi Susana C. , Karol Seth E. , Qu Chunxu , Brady Samuel W. , Gu Zhaohui , Yang Jun J. , Cheng Cheng , Downing James R. , Evans Williams E. , Relling Mary V. , Campana Dario , Mullighan Charles G. , Pui Ching-Hon
Published: April 2023

Supplementary Table S6
Supplementary Data-1 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy
Authors: Jeha Sima , Choi John , Roberts Kathryn G. , Pei Deqing , Coustan-Smith Elaine , Inaba Hiroto , Rubnitz Jeffrey E. , Ribeiro Raul C. , Gruber Tanja A. , Raimondi Susana C. , Karol Seth E. , Qu Chunxu , Brady Samuel W. , Gu Zhaohui , Yang Jun J. , Cheng Cheng , Downing James R. , Evans Williams E. , Relling Mary V. , Campana Dario , Mullighan Charles G. , Pui Ching-Hon
Published: April 2023

Supplementary Data Legend, Supplementary Table (S7) and Supplementary Figures (S1-S6)
Supplementary Data from Translational Activation of ATF4 through Mitochondrial Anaplerotic Metabolic Pathways Is Required for DLBCL Growth and Survival
Authors: Li Meng , Teater Matthew R. , Hong Jun Young , Park Noel R. , Duy Cihangir , Shen Hao , Wang Ling , Chen Zhengming , Cerchietti Leandro , Davidson Shawn M. , Lin Hening , Melnick Ari M.
Published: April 2023

Supplementary Data from Translational Activation of ATF4 through Mitochondrial Anaplerotic Metabolic Pathways Is Required for DLBCL Growth and Survival
Figure S9 from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

JWG-045 enhances the sensitivity of HER2+ breast cancer cells to trastuzumab through decreasing the proportion of cells in S phase, rather than increasing apoptotic cell death.
Data from Clinical Pharmacology and Determinants of Response to UCART19, an Allogeneic Anti-CD19 CAR-T Cell Product, in Adult B-cell Acute Lymphoblastic Leukemia
Authors: Dupouy Sandra , Marchiq Ibtissam , Derippe Thibaud , Almena-Carrasco Maria , Jozwik Agnieszka , Fouliard Sylvain , Adimy Yasmina , Geronimi Julia , Graham Charlotte , Jain Nitin , Maus Marcela V. , Mohty Mohamad , Boissel Nicolas , Teshima Takanori , Kato Koji , Benjamin Reuben , Balandraud Svetlana
Published: April 2023

Background:
UCART191 is an “off-the-shelf” genome-edited anti-CD19 chimeric antigen receptor (CAR)-T cell product, manufactured from unrelated healthy donor cells.
Methods:
UCART19 was administered to 25 adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) in the CALM trial. All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19. Given the allogeneic nature of UCART19, we analyzed the impact of lymphodepletion, HLA disparities, and host immune system reconstitution on its kinetics, along with other factors known to affect autologous CAR-T cell clinical pharmacology.
Results:
Responder patients (12/25) had higher UCART19 expansion (Cmax) and exposure (AUCTlast) than nonresponders (13/25), as measured by transgene levels in peripheral blood. The persistence of CAR+ T cells did not exceed 28 days in 10/25 patients and lasted beyond 42 days in 4/25. No significant correlation was found between UCART19 kinetics and administered cell dose, patient and product characteristics or HLA disparities. However, the number of prior lines of therapy and absence of alemtuzumab negatively impacted UCART19 expansion and persistence. Alemtuzumab exposure positively affected IL7 and UCART19 kinetics, while negatively correlating with host T lymphocyte AUC0-28.
Conclusions:
UCART19 expansion is a driver of response in adult patients with R/R B-ALL. These results shed light on the factors associated with UCART19 kinetics, which remain highly affected by the impact of alemtuzumab on IL7 and host-versus-graft rejection.
Significance:
First description of the clinical pharmacology of a genome-edited allogeneic anti-CD19 CAR-T cell product showing the crucial role of an alemtuzumab-based regimen in sustaining UCART19 expansion and persistence through increased IL7 availability and decreased host T lymphocyte population.
Data from IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines
Authors: Do-Thi Van Anh , Park Sang Min , Park Song Mi , Jeong Hye Jin , Cho Geunyoung , An Hyun-Jung , Kim Young Sang , Lee Hayyoung , Lee Jie-Oh
Published: April 2023

Tumor-associated macrophages (TAM) are involved in tumor progression, metastasis, and immunosuppression. Because TAMs are highly plastic and could alter their phenotypes to proinflammatory M1 in response to environmental stimuli, reeducating TAMs has emerged as a promising approach to overcoming the challenges of solid cancer treatment. This study investigated the effect of IL9 on macrophage M1 polarization and verified its antitumor potential to retrain TAMs and promote chemokine secretion. We demonstrated that IL9 stimulated macrophage proliferation and polarized them toward the proinflammatory M1 phenotype in an IFNγ-dependent manner. Tumor-localized IL9 also polarized TAMs toward M1 in vivo and made them release CCL3/4 and CXCL9/10 to recruit antitumor immune cells, including T and natural killer cells, into the tumor microenvironment. Furthermore, peritoneal treatment with recombinant IL9 delayed the growth of macrophage-enriched B16F10 melanoma and 4T1 breast cancer in syngeneic mice, although IL9 treatment did not reduce tumor growth in the absence of macrophage enrichment. These results demonstrate the efficacy of IL9 in macrophage polarization to trigger antitumor immunity.
Significance:
These findings clarified the effect of IL9 on macrophage M1 polarization and verified its antitumor potential through retraining TAMs and chemokine secretion.
Data from Detection of MET polysomy by next-generation sequencing and its clinical relevance for MET inhibitors
Authors: Sun Boyang , Qiu Tian , Zeng Xiaoling , Duan Jianchun , Bai Hua , Xu Jiachen , Li Jin , Li Junling , Hao Xuezhi , Liu Yutao , Lin Lin , Wang Hongyu , Zhang Xin , Zhong Jia , Wang Jie , Ying Jianming , Wang Zhijie
Published: April 2023

Abstract
Next-generation sequencing (NGS) has failed to detect mesenchymal epithelial transition factor gene (MET) polysomy in previous studies. We included three non-small cell lung cancer (NSCLC) cohorts in this retrospective study to establish new criteria for detecting MET polysomy and to explore the clinical relevance of MET polysomy. Cohort 1 included 53 patients whose tissues were available for both fluorescence in-situ hybridization (FISH) and NGS assays. Paired plasma and tissue samples were obtained from 261 patients with NSCLC as cohort 2. Cohort 3 included 46 patients with metastatic NSCLC, who presented with MET copy number gain assessed by NGS. Receiver operating characteristic (ROC) analysis demonstrated that a cut-off point of 2.3 copies achieved the maximum Youden index in discriminating polysomy from normal copy number. Compared with the FISH test for MET polysomy, the sensitivity, specificity, and agreement of NGS were 90%, 90%, and 96.2%, respectively. Following optimization using maximum somatic-allele-frequency (MSAF), the sensitivity and specificity of NGS for defining polysomy using plasma samples according to different ctDNA mutation frequencies were 42% and 63%. The concordance rate between tissue and plasma samples for detecting polysomy was 85%. Regarding the response to MET inhibitor, the median progression-free survival (PFS) of the MET amplification group was significantly higher than that of the polysomy group. The median PFS was similar between the polysomy and normal groups. Our results indicated that NGS may serve as an alternative method for detecting MET polysomy in NSCLC tissues. Moreover, patients with MET polysomy may not benefit from MET inhibitors.
Data from Analysis of N-linked Glycan Alterations in Tissue and Serum Reveals Promising Biomarkers for Intrahepatic Cholangiocarcinoma
Authors: Ochoa-Rios Shaaron , Blaschke Calvin R.K. , Wang Mengjun , Peterson Kendell D. , DelaCourt Andrew , Grauzam Stéphane Elie , Lewin David , Angel Peggi , Roberts Lewis R. , Drake Richard , Mehta Anand S.
Published: April 2023

There is an urgent need for the identification of reliable prognostic biomarkers for patients with intrahepatic cholangiocarcinoma (iCCA) and alterations in N-glycosylation have demonstrated an immense potential to be used as diagnostic strategies for many cancers, including hepatocellular carcinoma (HCC). N-glycosylation is one of the most common post-translational modifications known to be altered based on the status of the cell. N-glycan structures on glycoproteins can be modified based on the addition or removal of specific N-glycan residues, some of which have been linked to liver diseases. However, little is known concerning the N-glycan alterations that are associated with iCCA. We characterized the N-glycan modifications quantitatively and qualitatively in three cohorts, consisting of two tissue cohorts: a discovery cohort (n = 104 cases) and a validation cohort (n = 75), and one independent serum cohort consisting of patients with iCCA, HCC, or benign chronic liver disease (n = 67). N-glycan analysis in situ was correlated to tumor regions annotated on histopathology and revealed that bisected fucosylated N-glycan structures were specific to iCCA tumor regions. These same N-glycan modifications were significantly upregulated in iCCA tissue and serum relative to HCC and bile duct disease, including primary sclerosing cholangitis (PSC) (P < 0.0001). N-glycan modifications identified in iCCA tissue and serum were used to generate an algorithm that could be used as a biomarker of iCCA. We demonstrate that this biomarker algorithm quadrupled the sensitivity (at 90% specificity) of iCCA detection as compared with carbohydrate antigen 19-9, the current “gold standard” biomarker of CCA.
Significance:
This work elucidates the N-glycan alterations that occur directly in iCCA tissue and utilizes this information to discover serum biomarkers that can be used for the noninvasive detection of iCCA.
Data from Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew , Cam Maren , Gross Amy C , Raphael Benjamin J , Roberts Ryan D.
Published: April 2023

Abstract
Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNAs) are the genetic drivers of disease. Models around genomic instability conflict - it is unclear if osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization of the fitness landscape or an early catastrophic event followed by stable maintenance of an abnormal genome. We address this question by investigating SCNAs in >12,000 tumor cells obtained from human osteosarcomas using single cell DNA sequencing, with a degree of precision and accuracy not possible when inferring single cell states using bulk sequencing. Using the CHISEL algorithm, we inferred allele- and haplotype-specific SCNAs from this whole-genome single cell DNA sequencing data. Surprisingly, despite extensive structural complexity, these tumors exhibit a high degree of cell-cell homogeneity with little sub-clonal diversification. Longitudinal analysis of patient samples obtained at distant therapeutic time points (diagnosis, relapse) demonstrated remarkable conservation of SCNA profiles over tumor evolution. Phylogenetic analysis suggests that the majority of SCNAs were acquired early in the oncogenic process, with relatively few structure-altering events arising in response to therapy or during adaptation to growth in metastatic tissues. These data further support the emerging hypothesis that early catastrophic events, rather than sustained genomic instability, give rise to structural complexity, which is then preserved over long periods of tumor developmental time.
Multiple Germline Events Contribute to Cancer Development in Patients with Li-Fraumeni Syndrome
Authors: Subasri Vallijah , Light Nicholas , Kanwar Nisha , Brzezinski Jack , Luo Ping , Hansford Jordan R. , Cairney Elizabeth , Portwine Carol , Elser Christine , Finlay Jonathan L. , Nichols Kim E. , Alon Noa , Brunga Ledia , Anson Jo , Kohlmann Wendy , de Andrade Kelvin C. , Khincha Payal P. , Savage Sharon A. , Schiffman Joshua D. , Weksberg Rosanna , Pugh Trevor J. , Villani Anita , Shlien Adam , Goldenberg Anna , Malkin David
Published: April 2023

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer-predisposition disorder. Approximately 70% of individuals who fit the clinical definition of LFS harbor a pathogenic germline variant in the TP53 tumor suppressor gene. However, the remaining 30% of patients lack a TP53 variant and even among variant TP53 carriers, approximately 20% remain cancer-free. Understanding the variable cancer penetrance and phenotypic variability in LFS is critical to developing rational approaches to accurate, early tumor detection and risk-reduction strategies. We leveraged family-based whole-genome sequencing and DNA methylation to evaluate the germline genomes of a large, multi-institutional cohort of patients with LFS (n = 396) with variant (n = 374) or wildtype TP53 (n = 22). We identified alternative cancer-associated genetic aberrations in 8/14 wildtype TP53 carriers who developed cancer. Among variant TP53 carriers, 19/49 who developed cancer harbored a pathogenic variant in another cancer gene. Modifier variants in the WNT signaling pathway were associated with decreased cancer incidence. Furthermore, we leveraged the noncoding genome and methylome to identify inherited epimutations in genes including ASXL1, ETV6, and LEF1 that confer increased cancer risk. Using these epimutations, we built a machine learning model that can predict cancer risk in patients with LFS with an area under the receiver operator characteristic curve (AUROC) of 0.725 (0.633–0.810).

Significance:

Our study clarifies the genomic basis for the phenotypic variability in LFS and highlights the immense benefits of expanding genetic and epigenetic testing of patients with LFS beyond TP53. More broadly, it necessitates the dissociation of hereditary cancer syndromes as single gene disorders and emphasizes the importance of understanding these diseases in a holistic manner as opposed to through the lens of a single gene.