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JOINT Session - The Lymphoma Microenvironment and Its Impact on Therapy

PhD Trainee
Sponsor: Scientific Committee on Lymphoid Neoplasia||Scientific Committee on Transp Biology & Cellular Therapies
Program: Scientific Program
Hematology Disease Topics & Pathways:
Research, Biological therapies, Antibody Therapy, Hodgkin lymphoma, Clinical Practice (Health Services and Quality), Lymphomas, non-Hodgkin lymphoma, Translational Research, genomics, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Combination therapy, Diversity, Equity, and Inclusion (DEI) , T Cell lymphoma, Diseases, immune mechanism, indolent lymphoma, Therapies, aggressive lymphoma, Lymphoid Malignancies, metabolism, Biological Processes, pathogenesis
Sunday, December 11, 2022: 9:30 AM-11:05 AM
R02-R05 (Ernest N. Morial Convention Center)

Description:
Lymphoma B-cells exist within a complex milieu of immune and stromal cells that play a central role in lymphoma etiology direct cell-cell contact and/or the release of soluble factors. Inter-patient heterogeneity in lymphoma microenvironment characteristics have been linked with divergent outcomes following chemoimmunotherapy and are likely to be major determinants of response or resistance to modern immunotherapeutic approaches such as cell therapy and T-cell engagers. This session will highlight recent advances in the characterization of the lymphoma microenvironment and its association with therapeutic failure, with a focus on chimeric antigen receptor (CAR) T-cell therapy. 

Dr. Maher Gandhi will highlight recent advances in spatial imaging and single cell genomics that have provided new insights into how non-cancerous cells behave and interact within histologically distinct lymphoma subtypes. Lymphoma is a cancer of the immune system, in which malignant lymphoid cells co-exist within a sophisticated microenvironmental niche. Manipulating the environment to provide novel targeted therapeutics remains an unmet need.

Dr. Leandro Cerchietti will describe the distinct phenotypes of cancer associated fibroblasts (CAFs) in patients with B- and T-cell lymphomas. He will describe how these populations that include inflammatory and myofibroblastic CAFs are transcriptionally and epigenetically reprogrammed into cancer supporting entities. He will also describe the roles of CAFs throughout the course of disease, their unique role in older lymphoma patients, and potential therapeutic vulnerabilities that can be targeted for lymphoma immunotherapy. 

Dr. Frederick Locke will discuss how evidence from lymphoma patient samples collected on CAR-T cell clinical trials, and from patients treated with standard of care CAR-T, paint a picture of the lymphoma tumor mechanisms of resistance to CAR-T. He will describe the impact of tumor associated inflammatory signals and suppressive myeloid cells in the tumor microenvironment and periphery. Dr. Locke will also outline how the pretreatment immune contexture impacts efficacy, and the association between lymphoma cell genomic complexity and response to CAR-T therapy. 

Dr. Saad Kenderian will describe the impact of different components of the tumor microenvironment on outcomes of cellular immunotherapy for lymphoma. He will discuss how changes in cytokines, inhibitory myeloid cells, cancer associated fibroblasts, and extracellular vesicles interact with CAR-T cells and induce both toxicity and resistance to therapy. Lastly, he will review current efforts to modulate the tumor microenvironment in order to increase CAR-T cell safety and efficacy.

Chairs:
Michael R. Green, PhD, The University of Texas MD Anderson Cancer Center and Kelli MacDonald, PhD, QIMR Berghofer Medical Research Institute
Disclosures:
Green: Kite/Gilead: Research Funding; Sanofi: Research Funding; Allogene: Research Funding; Monte Rosa Therapeutics: Honoraria; Tessa Therapeutics: Honoraria; KDAc Therapeutics: Current equity holder in private company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.
Lymphoma B-cells exist within a complex milieu of immune and stromal cells that play a central role in lymphoma etiology direct cell-cell contact and/or the release of soluble factors. Inter-patient heterogeneity in lymphoma microenvironment characteristics have been linked with divergent outcomes following chemoimmunotherapy and are likely to be major determinants of response or resistance to modern immunotherapeutic approaches such as cell therapy and T-cell engagers. This session will highlight recent advances in the characterization of the lymphoma microenvironment and its association with therapeutic failure, with a focus on chimeric antigen receptor (CAR) T-cell therapy. 

Dr. Maher Gandhi will highlight recent advances in spatial imaging and single cell genomics that have provided new insights into how non-cancerous cells behave and interact within histologically distinct lymphoma subtypes. Lymphoma is a cancer of the immune system, in which malignant lymphoid cells co-exist within a sophisticated microenvironmental niche. Manipulating the environment to provide novel targeted therapeutics remains an unmet need.

Dr. Leandro Cerchietti will describe the distinct phenotypes of cancer associated fibroblasts (CAFs) in patients with B- and T-cell lymphomas. He will describe how these populations that include inflammatory and myofibroblastic CAFs are transcriptionally and epigenetically reprogrammed into cancer supporting entities. He will also describe the roles of CAFs throughout the course of disease, their unique role in older lymphoma patients, and potential therapeutic vulnerabilities that can be targeted for lymphoma immunotherapy. 

Dr. Frederick Locke will discuss how evidence from lymphoma patient samples collected on CAR-T cell clinical trials, and from patients treated with standard of care CAR-T, paint a picture of the lymphoma tumor mechanisms of resistance to CAR-T. He will describe the impact of tumor associated inflammatory signals and suppressive myeloid cells in the tumor microenvironment and periphery. Dr. Locke will also outline how the pretreatment immune contexture impacts efficacy, and the association between lymphoma cell genomic complexity and response to CAR-T therapy. 

Dr. Saad Kenderian will describe the impact of different components of the tumor microenvironment on outcomes of cellular immunotherapy for lymphoma. He will discuss how changes in cytokines, inhibitory myeloid cells, cancer associated fibroblasts, and extracellular vesicles interact with CAR-T cells and induce both toxicity and resistance to therapy. Lastly, he will review current efforts to modulate the tumor microenvironment in order to increase CAR-T cell safety and efficacy.

Maher K. Gandhi, PhD, FRACP, FRCPath

Blood Cancer Research Group, Mater Research, University of Queensland, Brisbane, QLD, Australia; Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia

Leandro Cerchietti, MD

Department of Medicine, Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York, NY

Frederick L. Locke, MD

Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL

Saad S. Kenderian, MD

Division of Hematology, Mayo Clinic, Rochester, MN

See more of: Scientific Program