# Discovery of myeloid immune features predictive of response to cancer immunotherapy in prostate cancer

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $38,188

## Abstract

PROJECT SUMMARY/ABSTRACT
Cancer immunotherapy has been a revolutionary antitumor treatment and is approved to treat a plethora of
cancer types. However, in solid tumors the response has been limited with only approximately 20 percent of
patients responding except for patients with high tumor burden as evidenced by microsatellite instability (MSI)
or mismatch repair deficiency (MMRD). The limited response is especially pronounced for prostate cancer. In
prostate cancer, the only currently approved therapy (except for MSI/MMRD patients) is sipuleucel-T, a
dendritic cell vaccine. Sipuleucel-T activates antigen presenting cells ex vivo before reinfusion where in vivo
activation of B and T cell responses are associated with response to the therapy. This immunogenic myeloid
and lymphoid cell interaction is just one example of a plethora of interactions which can be either immunogenic
or tolerogenic. Improved understanding of the role of myeloid compartment in pro- or anti-tumor activity will
allow for improved targeting of the myeloid compartment in combination immunotherapy strategies.
Immunosuppressive myeloid states can be observed both in the periphery and in the tumor microenvironment.
Peripheral monitoring of the immune system holds incredible potential due to the ease of monitoring and the
ability for longitudinal repeated sampling. To characterize the heterogeneity of the circulating myeloid
compartment, I used a genetic multiplexing strategy to simultaneously profile gene and protein expression
on single cells from ~700,000 peripheral blood mononuclear cells (PBMCs) from longitudinal sampling
of a metastatic castration resistant prostate cancer (mCRPC) cohort undergoing combined
immunotherapy. In my first aim, I propose to use this dataset to describe novel myeloid cell states in the
periphery and to investigate which states recapitulate in the tumor microenvironment and which states predict
clinical response to the immunotherapy. In my second aim, I will investigate how these myeloid cell states
interact with the lymphoid compartment to create an immunogenic or tolerogenic tumor response. My sponsor,
Dr. Jimmie Ye, has extensive expertise in single cell –omics for profiling the immune system in both auto-
immune and tumor contexts. My co-sponsor, Dr. Lawrence Fong, has made foundational discoveries in the
field of cancer immunotherapy with a particular focused on the mechanisms behind response to cancer
immunotherapy in genitourinary cancers, including prostate cancer. My co-sponsor, Dr. Matthew Spitzer, has
extensive expertise in the understanding the systemic response of the immune system to a tumor with a
particular focus in using mass cytometry for high dimensional single cell protein expression profiling. I will be
undergoing longitudinal clinical training in cancer immunotherapy with Dr. Lawrence Fong, who is the director
of the Cancer Immunotherapy Program at UCSF. Overall, this work will lay the foundation for improved
prediction of r...

## Key facts

- **NIH application ID:** 10141535
- **Project number:** 1F30CA257291-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elizabeth McCarthy
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,188
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141535

## Citation

> US National Institutes of Health, RePORTER application 10141535, Discovery of myeloid immune features predictive of response to cancer immunotherapy in prostate cancer (1F30CA257291-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141535. Licensed CC0.

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