# Spatial characterization of the tumor-immune microenvironment in SMARCB1-deficient epithelioid sarcomas

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $176,000

## Abstract

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 biolog...

## Key facts

- **NIH application ID:** 11074769
- **Project number:** 3U54CA274492-03S1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Christina S Leslie
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $176,000
- **Award type:** 3
- **Project period:** 2022-09-16 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11074769

## Citation

> US National Institutes of Health, RePORTER application 11074769, Spatial characterization of the tumor-immune microenvironment in SMARCB1-deficient epithelioid sarcomas (3U54CA274492-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11074769. Licensed CC0.

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