# The Effect of Tumor Burden on Peripheral cDC1 Activation and Functionality

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $38,451

## Abstract

PROJECT SUMMARY/ABSTRACT
Tumors disrupt the homeostasis of the immune system, altering immune cell composition and phenotype in the
tumor microenvironment (TME), lymph nodes, spleen, blood, and bone marrow. Mounting a de novo immune
response both peripherally and intratumorally is required for tumor clearance. Conventional type I dendritic cells
(cDC1s) are a critical component of this response and in the success of many immunotherapies. Tumors are
known to impair the function of cDCs in the TME, but questions about peripheral cDCs remain: how do
immunosuppressive mechanisms of tumors extend to cDCs in the spleen? In what ways do these
immunosuppressive pathways affect the CD8 T cell priming abilities of cDC1s? Answering these questions will
advance our understanding of cDC biology, tumor pathogenesis, and better inform effective immunotherapy
development. This proposal will test the hypothesis that soluble factors in the periphery of tumor-burdened
hosts alter the ability of cDC1s to prime de novo CD8 T cell responses to secondary infection. Aim 1 of this
proposal will determine the upstream mediators of impaired splenic cDC1 activation with tumor burden. Aim 2
will determine the mechanism of defective CD8 T cell priming by splenic cDC1s in the context of tumor burden.
This research approach will be carried out using a variety of methods including single-cell proteomic analysis
(flow cytometry and Mass Cytometry by Time of Flight (CyTOF)), imaging studies, ex vivo co-cultures, and in
vivo assays. These proposed studies will be some of the first mechanistic studies to assess ways that
tumor burden can alter peripheral cDC functionality. This could result in the novel discovery of pathways
important in the adaptive immune response to blood borne infections and result in furthering our understanding
of dendritic cell and T cell interactions. Translationally, this work will improve our understanding of cancer
patients’ susceptibility to infections and reveal potential therapeutic interventions. Further, this work will better
inform immunotherapy approaches for cancer treatment itself, especially in the adoptive cell therapy field –
specifically, how dendritic cell vaccines derived from peripheral cells or adoptive T cell therapy can be further
improved. This research project and fellowship training will be conducted at a top-funded research
institution, the University of California, San Francisco (UCSF), in the laboratories of Dr. Matthew Spitzer
and Dr. Lewis Lanier. Dr. Lanier has made extensive foundational discoveries in immune cell biology over the
course of his career. Dr. Spitzer is an investigator with expertise in systems cancer immunology approaches and
dendritic cell biology. These mentors and institution will provide a rich training environment for completion of the
proposed research and development of professional skills necessary for a continued academic research career.

## Key facts

- **NIH application ID:** 10442408
- **Project number:** 5F31CA265128-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rachel DeBarge
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,451
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442408

## Citation

> US National Institutes of Health, RePORTER application 10442408, The Effect of Tumor Burden on Peripheral cDC1 Activation and Functionality (5F31CA265128-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10442408. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*