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The Center for Tumor-Immune Systems Biology at MSKCC

MSKCC 肿瘤免疫系统生物学中心

基本信息

批准号：
10705726
负责人：
Christina S Leslie
金额：
$ 260.19万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-16 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705726
关键词：
Address Algorithmic Analysis Anti-Inflammatory Agents Astrocytes Award Blood Vessels Brain CD8-Positive T-Lymphocytes Cancer Biology Cancer Center Caspase Cell Death Cells Chromatin Clear cell renal cell carcinoma Colon Carcinoma Colorectal Cancer Complex Computational Biology Computing Methodologies Data Data Set Dendritic Cells Development Disease associated microglia Distal Ecosystem Education and Outreach Educational workshop Engineering Functional disorder Genetic Transcription Human Immune Immune response Immune system Immunofluorescence Immunologic Immunological Models Immunologics Immunology Immunotherapeutic agent Immunotherapy In complete remission Invaded Investigation Ligands Link Liver Lung Adenocarcinoma Malignant Neoplasms Mediating Melanoma Cell Memorial Sloan-Kettering Cancer Center Metastatic Neoplasm to Lymph Nodes Metastatic Neoplasm to the Leptomeninges Methods Mismatch Repair Mitochondria Modality Modeling Molecular Analysis Multiomic Data Organ Patients Process Refractory Regulator Genes Renal Cell Carcinoma Research Research Personnel Research Project Grants Resistance Resource Sharing Role Scientific Advances and Accomplishments Scientist Solid Neoplasm System Systems Biology T cell response T memory cell T-Lymphocyte Technology Therapeutic Training Training Activity Training Programs Tumor Immunity anti-cancer cancer care cancer cell cancer immunotherapeutics cancer immunotherapy clinical care computer studies design experimental study graduate student immune checkpoint blockade immunogenic immunogenic cell death improved innovation insight learning strategy lectures machine learning model malignant breast neoplasm mouse model multidisciplinary multiple omics novel novel strategies optical imaging programs receptor refractory cancer response standard of care success symposium tissue regeneration tool transcriptomics tumor tumor immunology tumor-immune system interactions undergraduate student

项目摘要

The Center for Tumor-Immune Systems Biology at MSKCC SUMMARY The advent of cancer immunotherapies based on immune checkpoint blockade (ICB) has revolutionized clinical care in multiple solid tumor types and demonstrated the power of the immune system to target and eliminate cancer cells. Despite these breakthroughs, the efficacy of ICB-based immunotherapy is limited to a subset of cancers, and even in tumors where ICB is now the standard of care, only a fraction of patients achieve durable complete responses. Addressing these limitations requires (1) improving our fundamental understanding of tumor-immune interactions in immunological contexts where current immunotherapies fail and (2) developing novel strategies for enhancing responses in contexts where they have only partial success. The Center for Tumor-Immune Systems Biology at MSKCC has assembled a multi-disciplinary team of leading investigators in computational biology, immunology, and cancer biology to tackle these challenges. The Center is organized around three Research Projects that integrate computational and experimental studies in mouse models and molecular analyses in patient tumors in both immunotherapy-resistant and -responsive contexts, exploiting novel machine learning modeling of single-cell multiome, highly multiplexed optical imaging using confocal immunofluorescence, and spatial transcriptomic data sets. We will investigate distinct immune microenvironments where cancers are refractory to ICB: metastatic colonization of the brain, an immune- privileged organ where the interplay of cancer cells, astrocytes, and different states of disease-associated microglia dictate modes of invasion (Project I); and mismatch-repair proficient primary colon cancer, where tumors reside in a tolerizing microenvironment and interact with complex cellular circuits of regulatory and conventional T cells, together with metastases to the lymph node and liver (Project II). We will also carry out a systems biology interrogation of cancer cell death mechanisms in models of ICB-responsive melanoma and renal cell carcinoma, based on findings that engineering mitochondrial damage-dependent but caspase- independent cell death elicits anti-cancer immunity and protection against tumor rechallenge (Project III). A Shared Resource Core will interact with all three Research Projects to develop computational methods and establish technologies for spatial analyses of the tumor-immune microenvironment. These studies will advance our fundamental understanding of tumor-immune ecosystems in ICB-refractory microenvironments and of immune responses to therapeutically induced immunogenic cancer cell death in ICB-responsive settings, ultimately leading to novel immunotherapeutic targets and combination strategies. Our team will build on the successes of our previous CSBC U54 Center award for the Center for Cancer Systems Immunology at MSKCC, which produced numerous high-impact studies at the forefront of systems biology and cancer immunology. Our Research Center will also carry out innovative outreach and training activities to disseminate research findings in tumor-immune systems biology and to train young scientists in this critical field.

肿瘤免疫系统生物学研究中心