# Quantitatively modeling immune responses to cancer

> **NIH NIH DP5** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $366,151

## Abstract

PROJECT SUMMARY/ABSTRACT
The immune system is a decentralized network of diverse white blood cells that is distributed across the entire
organism. Contributing to its complexity, the immune system has developed mechanisms by which it
remembers its prior experiences and is influenced by them. Recently, strategies to activate the immune system
of cancer patients to recognize and eliminate tumor cells have resulted in significant clinical progress. These
immunotherapies attempt to initiate new, potent immune responses in individuals with tumor burden. While
inspiring, the majority of cancer patients do not respond to these therapies, especially those with
adenocarcinomas, which are the most prevalent forms of cancer. Thus, there is a pressing need to understand
why these therapies often fail and use this knowledge to develop more effective strategies. One of the major
barriers to accomplishing this goal is our poor understanding of how the state of the immune system differs in
cancer patients compared to healthy individuals. While it is well appreciated that tumors actively evade
immune responses, we still do not understand how this context shapes the ability of the immune system to
initiate and execute new responses. This gap in our knowledge has partially resulted from insufficient methods
to measure and interpret the immune state. However, we have recently developed experimental and
computational methods capable of modeling the state of the immune system under any condition, identifying
how its behavior differs from the healthy setting. Therefore, in this proposal, we plan to apply these tools to
provide a comprehensive assessment of the immune state in tumor-bearing individuals. We will begin by
understanding how the immune system adapts its organization and behavior across the body during the
development and spread of a tumor. We will subsequently assess how immune cells that have experienced
tumor burden change their propensity to respond to new stimuli, including molecules that have potential as
immunotherapies. Lastly, we will reveal how the immune system responds differently to new challenges in
healthy versus tumor-bearing individuals. The result of these studies will be a comprehensive understanding of
how the experience of a tumor alters the behavior of the immune system. This knowledge will be essential for
the development of new immunotherapies for cancer by revealing which pathways of immune activation remain
functional or become enhanced in tumor-bearing individuals. Moreover, this proposal will reveal mechanisms
by which the immune system incorporates its prior knowledge when making decisions with broad implications
for all immunological processes including those in infection, autoimmunity and transplantation.

## Key facts

- **NIH application ID:** 9990574
- **Project number:** 5DP5OD023056-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Matthew Spitzer
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,151
- **Award type:** 5
- **Project period:** 2016-09-21 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990574

## Citation

> US National Institutes of Health, RePORTER application 9990574, Quantitatively modeling immune responses to cancer (5DP5OD023056-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9990574. Licensed CC0.

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