# Overcoming resistance to anti-PD1 immunotherapy

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2021 · $943,344

## Abstract

ABSTRACT
Novel immunotherapies for cancer are having a major clinical impact, in particular anti-PD-1
mAbs. However, the mechanisms that explain why a subset of patients responds to these
therapies while other patients do not remain incompletely understood. Our preliminary data
suggest that a baseline T cell-inflamed tumor microenvironment may be a predictive biomarker
for response to multiple immunotherapies. Combination immunotherapies may push clinical
efficacy in this subset of patients further. Our over-arching hypothesis is that germline
polymorphisms in the host, genomic features of the tumor cells, and the composition of
intestinal microbiota profoundly influence the extent of a spontaneous T cell response
against a patient's tumor, which in turn will determine the likelihood of response to
immunotherapy. Identifying molecular mechanisms for T cell exclusion should point towards
new therapeutic interventions that will expand the fraction of patients responding to anti-PD-1-
based immunotherapies. While our work to date has focused on melanoma, recent TCGA
analysis has indicated that many of the same principles apply to multiple additional cancer
types. Thus, a major goal of the proposed funding period will be to broaden our translational
research strategy to encompass patients with all cancer types being treated with anti-PD-1-
based immunotherapies. The output of this work is therefore anticipated to have profound
impact on cancer patient outcomes overall.

## Key facts

- **NIH application ID:** 10057358
- **Project number:** 5R35CA210098-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** THOMAS F GAJEWSKI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $943,344
- **Award type:** 5
- **Project period:** 2016-12-07 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057358

## Citation

> US National Institutes of Health, RePORTER application 10057358, Overcoming resistance to anti-PD1 immunotherapy (5R35CA210098-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10057358. Licensed CC0.

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