bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S7 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: November 2023

GSEA of genes associated with positive or negative correlation with radiographic response to ONC201 treatment.
Supplementary Figure S5 from Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer
Authors: Grillo Giacomo , Keshavarzian Tina , Linder Simon , Arlidge Christopher , Mout Lisanne , Nand Ankita , Teng Mona , Qamra Aditi , Zhou Stanley , Kron Ken J. , Murison Alex , Hawley James R. , Fraser Michael , van der Kwast Theodorus H. , Raj Ganesh V. , He Housheng Hansen , Zwart Wilbert , Lupien Mathieu
Published: November 2023

This figure showcases the enrichment of transposable element families in H3K27ac or H3K9kme3 ChIP-seq data generated in benign-like and prostate cancer cell lines. It also includes dCas9-KRAB expression patterns in all CRISPRi clonal cell lines used in this article
Table S13 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: November 2023

GSEA analysis of genes with significantly lower chromatin accessibility at promoters and enhancers and reduced gene expression in DIPG007 cells treated with ONC201 versus vehicle.
Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Authors: Buckbinder Leonard , St. Jean David J. , Tieu Trang , Ladd Brendon , Hilbert Brendan , Wang Weixue , Alltucker Jacob T. , Manimala Samantha , Kryukov Gregory V. , Brooijmans Natasja , Dowdell Gregory , Jonsson Philip , Huff Michael , Guzman-Perez Angel , Jackson Erica L. , Goncalves Marcus D. , Stuart Darrin D.
Published: November 2023

Includes Supplementary Tables S1 - S4 and Supplementary Figures S1 - S6
Table S1 from Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Venneti Sriram , Kawakibi Abed Rahman , Ji Sunjong , Waszak Sebastian M. , Sweha Stefan R. , Mota Mateus , Pun Matthew , Deogharkar Akash , Chung Chan , Tarapore Rohinton S. , Ramage Samuel , Chi Andrew , Wen Patrick Y. , Arrillaga-Romany Isabel , Batchelor Tracy T. , Butowski Nicholas A. , Sumrall Ashley , Shonka Nicole , Harrison Rebecca A. , de Groot John , Mehta Minesh , Hall Matthew D. , Daghistani Doured , Cloughesy Timothy F. , Ellingson Benjamin M. , Beccaria Kevin , Varlet Pascale , Kim Michelle M. , Umemura Yoshie , Garton Hugh , Franson Andrea , Schwartz Jonathan , Jain Rajan , Kachman Maureen , Baum Heidi , Burant Charles F. , Mottl Sophie L. , Cartaxo Rodrigo T. , John Vishal , Messinger Dana , Qin Tingting , Peterson Erik , Sajjakulnukit Peter , Ravi Karthik , Waugh Alyssa , Walling Dustin , Ding Yujie , Xia Ziyun , Schwendeman Anna , Hawes Debra , Yang Fusheng , Judkins Alexander R. , Wahl Daniel , Lyssiotis Costas A. , de la Nava Daniel , Alonso Marta M. , Eze Augustine , Spitzer Jasper , Schmidt Susanne V. , Duchatel Ryan J. , Dun Matthew D. , Cain Jason E. , Jiang Li , Stopka Sylwia A. , Baquer Gerard , Regan Michael S. , Filbin Mariella G. , Agar Nathalie Y.R. , Zhao Lili , Kumar-Sinha Chandan , Mody Rajen , Chinnaiyan Arul , Kurokawa Ryo , Pratt Drew , Yadav Viveka N. , Grill Jacques , Kline Cassie , Mueller Sabine , Resnick Adam , Nazarian Javad , Allen Joshua E. , Odia Yazmin , Gardner Sharon L. , Koschmann Carl
Published: November 2023

Baseline characteristics of ONC201-treated H3K27M-DMG patients included in analysis.
Supplementary Table S2 from MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

PTMScan data tables
Supplementary Table S1 from MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

Hematological parameters in CD-1 mice treated with MRTX11719
Supplementary Materials and Methods from MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

Materials and methods related to supplemental data
Supplementary Figure S5 from MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

Co-culture experiments with MTAP-expressing fibroblasts
Supplementary Figure S2 from MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J. David , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Jänne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

Supplemental biochemical and cellular characterization of MRTX1719
Supplementary Table S4 from BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: November 2023

Supplementary Table S4 contains the sequences of all qPCR primers used in this study.
Supplementary Table S2 from BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: November 2023

Supplementary Table S2 contains the full list of genes involved in the arrayed CRISPR screening and the top candidate genes detected by this screening, as well as their link to seven potentially druggable pathways.
Supplementary Table S1 from BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: November 2023

Supplementary Table S1 contains the full list of genes involved in the pooled CRISPR screening and the top candidate genes selected from this screening.
Supplementary Figure S1 from BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: November 2023

Supplementary Figure S1 lists pathways that connect candidate genes selected form the array CRISPR screening and the potential mechanisms for DC antigen cross-presentation enhancement by BCL2 inhibition including apoptosis and autophagy.
Data from Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial
Authors: Cascone Tina , Kar Gozde , Spicer Jonathan D. , García-Campelo Rosario , Weder Walter , Daniel Davey B. , Spigel David R. , Hussein Maen , Mazieres Julien , Oliveira Julio , Yau Edwin H. , Spira Alexander I. , Anagnostou Valsamo , Mager Raymond , Hamid Oday , Cheng Lin-Yang , Zheng Ying , Blando Jorge , Tan Tze Heng , Surace Michael , Rodriguez-Canales Jaime , Gopalakrishnan Vancheswaran , Sellman Bret R. , Grenga Italia , Soo-Hoo Yee , Kumar Rakesh , McGrath Lara , Forde Patrick M.
Published: November 2023

Abstract
Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti–PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.
Significance:
A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function.

See related commentary by Cooper and Yu, p. 2306.

This article is featured in Selected Articles from This Issue, p. 2293
Data from BCL2 Inhibition Reveals a Dendritic Cell–Specific Immune Checkpoint That Controls Tumor Immunosurveillance
Authors: Zhao Liwei , Liu Peng , Mao Misha , Zhang Shuai , Bigenwald Camille , Dutertre Charles-Antoine , Lehmann Christian H.K. , Pan Hui , Paulhan Nicolas , Amon Lukas , Buqué Aitziber , Yamazaki Takahiro , Galluzzi Lorenzo , Kloeckner Benoit , Silvin Aymeric , Pan Yuhong , Chen Hui , Tian Ai-Ling , Ly Pierre , Dudziak Diana , Zitvogel Laurence , Kepp Oliver , Kroemer Guido
Published: November 2023

Abstract
We developed a phenotypic screening platform for the functional exploration of dendritic cells (DC). Here, we report a genome-wide CRISPR screen that revealed BCL2 as an endogenous inhibitor of DC function. Knockout of BCL2 enhanced DC antigen presentation and activation as well as the capacity of DCs to control tumors and to synergize with PD-1 blockade. The pharmacologic BCL2 inhibitors venetoclax and navitoclax phenocopied these effects and caused a cDC1-dependent regression of orthotopic lung cancers and fibrosarcomas. Thus, solid tumors failed to respond to BCL2 inhibition in mice constitutively devoid of cDC1, and this was reversed by the infusion of DCs. Moreover, cDC1 depletion reduced the therapeutic efficacy of BCL2 inhibitors alone or in combination with PD-1 blockade and treatment with venetoclax caused cDC1 activation, both in mice and in patients. In conclusion, genetic and pharmacologic BCL2 inhibition unveils a DC-specific immune checkpoint that restrains tumor immunosurveillance.
Significance:
BCL2 inhibition improves the capacity of DCs to stimulate anticancer immunity and restrain cancer growth in an immunocompetent context but not in mice lacking cDC1 or mature T cells. This study indicates that BCL2 blockade can be used to sensitize solid cancers to PD-1/PD-L1–targeting immunotherapy.

This article is featured in Selected Articles from This Issue, p. 2293
Supplementary Figure 1 from EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade
Authors: Tabasum Saba , Thapa Dinesh , Giobbie-Hurder Anita , Weirather Jason L. , Campisi Marco , Schol Pieter J. , Li Xiaoyu , Li Jingjing , Yoon Charles H. , Manos Michael P. , Barbie David A. , Hodi F. Stephen
Published: November 2023

EDIL3 antibody response to Ipi-Bev therapy in metastatic melanoma patients.
Supplementary Data from EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade
Authors: Tabasum Saba , Thapa Dinesh , Giobbie-Hurder Anita , Weirather Jason L. , Campisi Marco , Schol Pieter J. , Li Xiaoyu , Li Jingjing , Yoon Charles H. , Manos Michael P. , Barbie David A. , Hodi F. Stephen
Published: November 2023

Gene expression (TPM) data from the bulk RNA-seq analysis.
Supplementary Figure 5 from Targeted Inhibition of lncRNA Malat1 Alters the Tumor Immune Microenvironment in Preclinical Syngeneic Mouse Models of Triple-Negative Breast Cancer
Authors: Adewunmi Oluwatoyosi , Shen Yichao , Zhang Xiang H.-F. , Rosen Jeffrey M.
Published: November 2023

Supplementary Figure 5
Supplementary Figure 2 from Targeted Inhibition of lncRNA Malat1 Alters the Tumor Immune Microenvironment in Preclinical Syngeneic Mouse Models of Triple-Negative Breast Cancer
Authors: Adewunmi Oluwatoyosi , Shen Yichao , Zhang Xiang H.-F. , Rosen Jeffrey M.
Published: November 2023

Supplementary Figure 2
Supplementary Figure 1 from Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function
Authors: Zhang Caimei , Kadu Siddhant , Xiao Yansen , Johnson Omar , Kelly Andre , O'Connor Roddy S. , Lai Meizan , Kong Hong , Srivatsa Sriram , Tai Victoria , Greenblatt Eli , Holmes Matthew , Riley James L. , June Carl H. , Sheppard Neil C.
Published: November 2023

Figure S1. mbIL-21 structure and the effect of K562 expressing CD40 on NK cell expansion
Supplementary Table 2 from Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
Authors: Lee Yi-Mei , Hsu Chia-Lang , Chen Yu-Hsin , Ou Da-Liang , Hsu Chiun , Tan Ching-Ting
Published: November 2023

a list of harvested tongue samples in this study
Supplementary Video 1 (RTX) from slan+ Monocytes Kill Cancer Cells Coated in Therapeutic Antibody by Trogoptosis
Authors: Finotti Giulia , Pietronigro Enrica , Balanzin Camillo , Lonardi Silvia , Constantin Gabriela , Chao Mark P. , Tecchio Cristina , Vermi William , Cassatella Marco A.
Published: November 2023

Supplementary Video 1
Supplementary Figure 2 from slan+ Monocytes Kill Cancer Cells Coated in Therapeutic Antibody by Trogoptosis
Authors: Finotti Giulia , Pietronigro Enrica , Balanzin Camillo , Lonardi Silvia , Constantin Gabriela , Chao Mark P. , Tecchio Cristina , Vermi William , Cassatella Marco A.
Published: November 2023

Phagocytosis of RTX- and/or 5F9/Magrolimab-coated Daudi cells by in vitro generated slan+- macrophages
Data from EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade
Authors: Tabasum Saba , Thapa Dinesh , Giobbie-Hurder Anita , Weirather Jason L. , Campisi Marco , Schol Pieter J. , Li Xiaoyu , Li Jingjing , Yoon Charles H. , Manos Michael P. , Barbie David A. , Hodi F. Stephen
Published: November 2023

Abstract
Immune checkpoint blockade (ICB) has become the standard of care for several solid tumors. Multiple combinatorial approaches have been studied to improve therapeutic efficacy. The combination of antiangiogenic agents and ICB has demonstrated efficacy in several cancers. To improve the mechanistic understanding of synergies with these treatment modalities, we performed screens of sera from long-term responding patients treated with ipilimumab and bevacizumab. We discovered a high-titer antibody response against EGF-like repeats and discoidin I–like domains protein 3 (EDIL3) that correlated with favorable clinical outcomes. EDIL3 is an extracellular protein, previously identified as a marker of poor prognosis in various malignancies. Our Tumor Immune Dysfunction and Exclusion analysis predicted that EDIL3 was associated with immune exclusion signatures for cytotoxic immune cell infiltration and nonresponse to ICB. Cancer-associated fibroblasts (CAF) were predicted as the source of EDIL3 in immune exclusion–related cells. Furthermore, The Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) and CheckMate 064 data analyses correlated high levels of EDIL3 with increased pan-fibroblast TGFβ response, enrichment of angiogenic signatures, and induction of epithelial-to-mesenchymal transition. Our in vitro studies validated EDIL3 overexpression and TGFβ regulation in patient-derived CAFs. In pretreatment serum samples from patients, circulating levels of EDIL3 were associated with circulating levels of VEGF, and like VEGF, EDIL3 increased the angiogenic abilities of patient-derived tumor endothelial cells (TEC). Mechanistically, three-dimensional microfluidic cultures and two-dimensional transmigration assays with TEC endorsed EDIL3-mediated disruption of the lymphocyte function-associated antigen-1 (LFA-1)–ICAM-1 interaction as a possible means of T-cell exclusion. We propose EDIL3 as a potential target for improving the transendothelial migration of immune cells and efficacy of ICB therapy.
Data from Targeted Inhibition of lncRNA Malat1 Alters the Tumor Immune Microenvironment in Preclinical Syngeneic Mouse Models of Triple-Negative Breast Cancer
Authors: Adewunmi Oluwatoyosi , Shen Yichao , Zhang Xiang H.-F. , Rosen Jeffrey M.
Published: November 2023

Abstract
Long noncoding RNAs (lncRNA) play an important role in gene regulation in both normal tissues and cancer. Targeting lncRNAs is a promising therapeutic approach that has become feasible through the development of gapmer antisense oligonucleotides (ASO). Metastasis-associated lung adenocarcinoma transcript (Malat1) is an abundant lncRNA whose expression is upregulated in several cancers. Although Malat1 increases the migratory and invasive properties of tumor cells, its role in the tumor microenvironment (TME) is still not well defined. We explored the connection between Malat1 and the tumor immune microenvironment (TIME) using several immune-competent preclinical syngeneic Tp53-null triple-negative breast cancer (TNBC) mouse models that mimic the heterogeneity and immunosuppressive TME found in human breast cancer. Using a Malat1 ASO, we were able to knockdown Malat1 RNA expression resulting in a delay in primary tumor growth, decreased proliferation, and increased apoptosis. In addition, immunophenotyping of tumor-infiltrating lymphocytes revealed that Malat1 inhibition altered the TIME, with a decrease in immunosuppressive tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) as well as an increase in cytotoxic CD8+ T cells. Malat1 depletion in tumor cells, TAMs, and MDSCs decreased immunosuppressive cytokine/chemokine secretion whereas Malat1 inhibition in T cells increased inflammatory secretions and T-cell proliferation. Combination of a Malat1 ASO with chemotherapy or immune checkpoint blockade (ICB) improved the treatment responses in a preclinical model. These studies highlight the immunostimulatory effects of Malat1 inhibition in TNBC, the benefit of a Malat1 ASO therapeutic, and its potential use in combination with chemotherapies and immunotherapies.
Supplementary Tables S1, S2, S3 from IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies
Authors: Lancman Guido , Parsa Kian , Kotlarz Krzysztof , Avery Lisa , Lurie Alaina , Lieberman-Cribbin Alex , Cho Hearn Jay , Parekh Samir S. , Richard Shambavi , Richter Joshua , Rodriguez Cesar , Rossi Adriana , Sanchez Larysa J. , Thibaud Santiago , Jagannath Sundar , Chari Ajai
Published: November 2023

Supplementary Table S1: Description of all grade 3-5 infections. Supplementary Table S2: Infection rates per time period from start of bispecific antibody, divided by presumed microbiology. Rates are presented as infections per patient-year (95% confidence intervals). Supplementary table S3: Univariate logistic regression analysis of baseline risk factors for grade 3-5 infections among responders.
Figure S3 from IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies
Authors: Lancman Guido , Parsa Kian , Kotlarz Krzysztof , Avery Lisa , Lurie Alaina , Lieberman-Cribbin Alex , Cho Hearn Jay , Parekh Samir S. , Richard Shambavi , Richter Joshua , Rodriguez Cesar , Rossi Adriana , Sanchez Larysa J. , Thibaud Santiago , Jagannath Sundar , Chari Ajai
Published: November 2023

Swimmer’s plot for bacterial grade 3-5 infections during the study period, divided into ‘On-IVIg’ and “Off-IVIg’ periods
Table S2 from Clinical Correlates of Venetoclax-Based Combination Sensitivities to Augment Acute Myeloid Leukemia Therapy
Authors: Eide Christopher A. , Kurtz Stephen E. , Kaempf Andy , Long Nicola , Joshi Sunil Kumar , Nechiporuk Tamilla , Huang Ariane , Dibb Charles A. , Taylor Akosha , Bottomly Daniel , McWeeney Shannon K. , Minnier Jessica , Lachowiez Curtis A. , Saultz Jennifer N. , Swords Ronan T. , Agarwal Anupriya , Chang Bill H. , Druker Brian J. , Tyner Jeffrey W.
Published: November 2023

Comparison of feature balance between training and test cohorts
Data from Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells
Authors: Nelde Annika , Schuster Heiko , Heitmann Jonas S. , Bauer Jens , Maringer Yacine , Zwick Melissa , Volkmer Jens-Peter , Chen James Y. , Stanger Anna M. Paczulla , Lehmann Ariane , Appiah Bismark , Märklin Melanie , Rücker-Braun Elke , Salih Helmut R. , Roerden Malte , Schroeder Sarah M. , Häring Max-Felix , Schlosser Andreas , Schetelig Johannes , Schmitz Marc , Boerries Melanie , Köhler Natalie , Lengerke Claudia , Majeti Ravindra , Weissman Irving L. , Rammensee Hans-Georg , Walz Juliane S.
Published: November 2023

Abstract
Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. LSC-targeting therapies may thus improve outcome of patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens that induce T-cell responses allowing for immune surveillance of AML. Using a mass spectrometry–based immunopeptidomics approach, we characterized the antigenic landscape of patient LSCs and identified AML- and AML/LSC-associated HLA-presented antigens absent from normal tissues comprising nonmutated peptides, cryptic neoepitopes, and neoepitopes of common AML driver mutations of NPM1 and IDH2. Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. Together, these antigens shared among AML and LSCs represent prime targets for T cell–based therapies with potential of eliminating residual LSCs in patients with AML.
Significance:
The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. This study identifies and functionally validates LSC-associated HLA class I and HLA class II–presented antigens, paving the way to the development of LSC-directed T cell–based immunotherapeutic approaches for patients with AML.

See related commentary by Ritz, p. 430.

This article is featured in Selected Articles from This Issue, p. 419
Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Lee Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL.

Significance:

Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient.
Survey of euthanasia methods used in neotropical chiropterans in São Paulo State, Brazil
Authors: Lauri Liura Sanchez , Souza Alex Junior Souza de , Scheffer Karin Corrêa , Mori Enio , Sá Lilian Rose Marques de
Published: November 2023

Zoonotic Surveillance Divisions (ZSDs) rescue and euthanize bats in contact with humans. The euthanasia procedure should be conducted safely for the animal and caretaker and minimal stress for the animal is important. The objectives of this study were: i. evaluate the methods of euthanasia used by ZSDs in the State of São Paulo; ii. compare the methods with national and international guidelines for animal euthanasia practices; iii. assess the methodologies considering taxonomy and eating habits of the main bat species, and iv. propose standardization of euthanasia procedures. Sixty-five ZSDs locations received an online questionnaire or were contacted by telephone and 33 ZSDs (50.8%) responded and are distributed in 11 mesoregions in the state to remain anonymous. The euthanasia methods were divided into chemical (injectable or inhalation), physical, or mixed methods. Bat specimens (n = 550) were identified and classified to evaluate the main genera found in the state. The location of the ZSD, species, eating habits, and the method of euthanasia used were analyzed. The specimens by bat families were Molossidae (n = 340), Phyllostomidae (n = 171), and Vespertilionidae (n = 39). Chemical methods were used in 25 ZSDs (75.75%), physical in 5 (15.15%), and mixed in 3 (9.09%). There is no uniformity or standardization in bat euthanasia methods used by ZSDs, although most are based on acceptable chemical methods. It was proposed an algorithm to assist the veterinarian in choosing the method of euthanasia for bats that will allow standardizing euthanasia procedures for this species, considering physiological differences, and respecting technical, bioethical, and animal welfare guidelines.
Circuits in the motor cortex explain oscillatory responses to transcranial magnetic stimulation
Authors: Haggie Lysea , Besier Thor , McMorland Angus
Published: November 2023

Transcranial magnetic stimulation (TMS) is a popular method used to investigate brain function. Stimulation over the motor cortex evokes muscle contractions known as motor evoked potentials (MEPs) and also high-frequency volleys of electrical activity measured in the cervical spinal cord. The physiological mechanisms of these experimentally derived responses remain unclear, but it is thought that the connections between circuits of excitatory and inhibitory neurons play a vital role. Using a spiking neural network model of the motor cortex, we explained the generation of waves of activity, so called ‘I-waves’, following cortical stimulation. The model reproduces a number of experimentally known responses including direction of TMS, increased inhibition, and changes in strength. Using populations of thousands of neurons in a model of cortical circuitry we showed that the cortex generated transient oscillatory responses without any tuning, and that neuron parameters such as refractory period and delays influenced the pattern and timing of those oscillations. By comparing our network with simpler, previously proposed circuits, we explored the contributions of specific connections and found that recurrent inhibitory connections are vital in producing later waves that significantly impact the production of motor evoked potentials in downstream muscles (Thickbroom, 2011). This model builds on previous work to increase our understanding of how complex circuitry of the cortex is involved in the generation of I-waves.
Weighting the structural connectome: Exploring its impact on network properties and predicting cognitive performance in the human brain
Authors: Gast Hila , Assaf Yaniv
Published: November 2023

Brain function does not emerge from isolated activity, but rather from the interactions and exchanges between neural elements that form a network known as the connectome. The human connectome consists of structural and functional aspects. The structural connectome (SC) represents the anatomical connections, and the functional connectome represents the resulting dynamics that emerge from this arrangement of structures. As there are different ways of weighting these connections, it is important to consider how such different approaches impact study conclusions. Here, we propose that different weighted connectomes result in varied network properties, and while neither superior the other, selection might affect interpretation and conclusions in different study cases. We present three different weighting models, namely, number of streamlines (NOS), fractional anisotropy (FA), and axon diameter distribution (ADD), to demonstrate these differences. The later, is extracted using recently published AxSI method and is first compared to commonly used weighting methods. Moreover, we explore the functional relevance of each weighted SC, using the Human Connectome Project (HCP) database. By analyzing intelligence-related data, we develop a predictive model for cognitive performance based on graph properties and the National Institutes of Health (NIH) toolbox. Results demonstrate that the ADD SC, combined with a functional subnetwork model, outperforms other models in estimating cognitive performance.
Linking fast and slow: The case for generative models
Authors: Medrano Johan , Friston Karl , Zeidman Peter
Published: November 2023

A pervasive challenge in neuroscience is testing whether neuronal connectivity changes over time due to specific causes, such as stimuli, events, or clinical interventions. Recent hardware innovations and falling data storage costs enable longer, more naturalistic neuronal recordings. The implicit opportunity for understanding the self-organised brain calls for new analysis methods that link temporal scales: from the order of milliseconds over which neuronal dynamics evolve, to the order of minutes, days, or even years over which experimental observations unfold. This review article demonstrates how hierarchical generative models and Bayesian inference help to characterise neuronal activity across different time scales. Crucially, these methods go beyond describing statistical associations among observations and enable inference about underlying mechanisms. We offer an overview of fundamental concepts in state-space modeling and suggest a taxonomy for these methods. Additionally, we introduce key mathematical principles that underscore a separation of temporal scales, such as the slaving principle, and review Bayesian methods that are being used to test hypotheses about the brain with multiscale data. We hope that this review will serve as a useful primer for experimental and computational neuroscientists on the state of the art and current directions of travel in the complex systems modelling literature.
NBS-SNI, an extension of the network-based statistic: Abnormal functional connections between important structural actors
Authors: Normand Francis , Gajwani Mehul , Côté Daniel C. , Allard Antoine
Published: November 2023

Elucidating the coupling between the structure and the function of the brain and its development across maturation has attracted a lot of interest in the field of network neuroscience in the last 15 years. Mounting evidence supports the hypothesis that the onset of certain brain disorders is linked with the interplay between the structural architecture of the brain and its functional processes, often accompanied with unusual connectivity features. This paper introduces a method called the network-based statistic–simultaneous node investigation (NBS-SNI) that integrates both representations into a single framework, and identifies connectivity abnormalities in case-control studies. With this method, significance is given to the properties of the nodes, as well as to their connections. This approach builds on the well-established network-based statistic (NBS) proposed in 2010. We uncover and identify the regimes in which NBS-SNI offers a gain in statistical resolution to identify a contrast of interest using synthetic data. We also apply our method on two real case-control studies, one consisting of individuals diagnosed with autism and the other consisting of individuals diagnosed with early psychosis. Using NBS-SNI and node properties such as the closeness centrality and local information dimension, we found hypo- and hyperconnected subnetworks and show that our method can offer a 9 percentage points gain in prediction power over the standard NBS.
Predictability of cortico-cortical connections in the mammalian brain
Authors: Molnár Ferenc , Horvát Szabolcs , Ribeiro Gomes Ana R. , Martinez Armas Jorge , Molnár Botond , Ercsey-Ravasz Mária , Knoblauch Kenneth , Kennedy Henry , Toroczkai Zoltan
Published: November 2023

Despite a five order of magnitude range in size, the brains of mammals share many anatomical and functional characteristics that translate into cortical network commonalities. Here we develop a machine learning framework to quantify the degree of predictability of the weighted interareal cortical matrix. Partial network connectivity data were obtained with retrograde tract-tracing experiments generated with a consistent methodology, supplemented by projection length measurements in a nonhuman primate (macaque) and a rodent (mouse). We show that there is a significant level of predictability embedded in the interareal cortical networks of both species. At the binary level, links are predictable with an area under the ROC curve of at least 0.8 for the macaque. Weighted medium and strong links are predictable with an 85%–90% accuracy (mouse) and 70%–80% (macaque), whereas weak links are not predictable in either species. These observations reinforce earlier observations that the formation and evolution of the cortical network at the mesoscale is, to a large extent, rule based. Using the methodology presented here, we performed imputations on all area pairs, generating samples for the complete interareal network in both species. These are necessary for comparative studies of the connectome with minimal bias, both within and across species.
The evolution of whole-brain turbulent dynamics during recovery from traumatic brain injury
Authors: Martínez-Molina Noelia , Escrichs Anira , Sanz-Perl Yonatan , Sihvonen Aleksi J. , Särkämö Teppo , Kringelbach Morten L. , Deco Gustavo
Published: November 2023

It has been previously shown that traumatic brain injury (TBI) is associated with reductions in metastability in large-scale networks in resting-state fMRI (rsfMRI). However, little is known about how TBI affects the local level of synchronization and how this evolves during the recovery trajectory. Here, we applied a novel turbulent dynamics framework to investigate whole-brain dynamics using an rsfMRI dataset from a cohort of moderate to severe TBI patients and healthy controls (HCs). We first examined how several measures related to turbulent dynamics differ between HCs and TBI patients at 3, 6, and 12 months post-injury. We found a significant reduction in these empirical measures after TBI, with the largest change at 6 months post-injury. Next, we built a Hopf whole-brain model with coupled oscillators and conducted in silico perturbations to investigate the mechanistic principles underlying the reduced turbulent dynamics found in the empirical data. A simulated attack was used to account for the effect of focal lesions. This revealed a shift to lower coupling parameters in the TBI dataset and, critically, decreased susceptibility and information-encoding capability. These findings confirm the potential of the turbulent framework to characterize longitudinal changes in whole-brain dynamics and in the reactivity to external perturbations after TBI.
Description of the early shell morphology of three species of Pectinidae (Mollusca: Bivalvia) from Argentina
Authors: OVIEDO LORELEY , PASTORINO GUIDO
Published: November 2023

We describe the shell morphology of the prodissoconch and early postlarval shell of Aequipecten tehuelchus (d’Orbigny), Flexopecten felipponei (Dall), and Zygochlamys patagonica (King) from the southern coast of Argentina. Aequipecten tehuelchus has a nepioconch microsculpture with fine, dense, and regularly distributed pits. The byssal notch is initially deep and narrow but becomes sinuous at the beginning of the post-nepioconch. The nepioconch of Zygochlamys patagonica has antimarginal riblets; the byssal notch is wider than in A. tehuelchus and does not present the sinuosity observed in the other species. The microsculpture of the nepioconchs of F. felipponei and A. tehuelchus is indistinguishable. The earliest differentiation between the two species appears with the post-nepionic left valve, in which A. tehuelchus exhibits between 15 and 20 primary ribs while F. felipponei displays 28 to 34 faint folds. Zygochlamys patagonica shows 21 to 31 primary and secondary ribs. The taxonomic status of the three species is discussed in light of these findings and with respect to current adult-shell taxonomy and genetic analyses.
Correction of mistakes. II. New taxonomic position of Chaetocladius (Amblycladius) amurensis Makarchenko et Makarchenko (Diptera: Chironomidae: Orthocladiinae) from the Russian Far East, with redescription of species
Authors: MAKARCHENKO EUGENYI A. , YAVORSKAYA NADEZHDA M.
Published: November 2023

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Phosphoproteomics and morphology of stored human red blood cells treated by protein tyrosine phosphatases inhibitor
Authors: Bardyn Manon , Crettaz David , Rappaz Benjamin , Hamelin Romain , Armand Florence , Tissot Jean-Daniel , Turcatti Gerardo , Prudent Michel
Published: November 2023

The process of protein phosphorylation is involved in numerous cell functions. In particular, phosphotyrosine (pY) has been reported to play a role in red blood cell (RBC) functions, including the cytoskeleton organization. During their storage before transfusion, RBCs suffer from storage lesions that affect their energy metabolism and morphology. This study investigated the relationship between pY and the storage lesions. To do so, RBCs were treated (in the absence of calcium) with a protein tyrosine phosphatase inhibitor (orthovanadate [OV]) to stimulate phosphorylation and with 3 selective kinase inhibitors (KIs). Erythrocyte membrane proteins were studied by western blot analyses and phosphoproteomics (data are available via ProteomeXchange with identifier PXD039914) and cell morphology by digital holographic microscopy. The increase of pY triggered by OV treatment (inducing a global downregulation of pS and pT) disappeared during the storage. Phosphoproteomic analysis identified 609 phosphoproteins containing 1752 phosphosites, of which 41 pY were upregulated and 2 downregulated by OV. After these phosphorylation processes, the shape of RBCs shifted from discocytes to spherocytes, and the addition of KIs partially inhibited this transition. The KIs modulated either pY or pS and pT via diverse mechanisms related to cell shape, thereby affecting RBC morphology. The capacity of RBCs to maintain their function is central in transfusion medicine, and the presented results contribute to a better understanding of RBC biology.