# Targeting the Immune Onco-GPCRome  as a Novel Multimodal Cancer Immunotherapy Strategy

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,401

## Abstract

ABSTRACT
Recent advances in checkpoint blockade immunotherapy (CBI) inhibiting programmed death-1 (PD-1) and
cytotoxic T-lymphocyte antigen-4 (CTLA-4) have revolutionized cancer treatment. However, the limited response
rates in most cancers suggest that new approaches and targets are clearly needed to fully elucidate the
underlying biology of dysfunctional and exhausted CD8 T cells in cancer and achieve durable responses (cure).
G-protein coupled receptors (GPCRs) are the most intensively studied drug targets since they play key roles in
many physiological processes, and they have remained longstanding favorable pharmacological targets. Here,
we plan to first use novel computational approaches analyzing multiple single cell RNAseq databases to
deconvolute T cell heterogeneity in order to generate a transcriptomic GPCR signature for tumor infiltrating T
cells. Preliminary data shows an upregulation of prostaglandin receptors, EP2 and EP4, on exhausted T cells,
suggesting that these GPCRs that are coupled to the G protein Gs, and their downstream signaling cascades
may be dampening anti-tumor cytotoxicity of CD8 T cells, leading to exhaustion. We hypothesize that activation
of EP2 and EP4 on CD8 T cells and the subsequent Gs signaling leads to decreased cytotoxic and migratory
activity that nullifies the effectiveness of PD-1 and CTLA-4 blockade. Put together, EP2 and EP4 may represent
promising candidates as immune checkpoints that can be targeted in combination with CBI as part of novel
multimodality precision immunotherapy approach to reactivate the immune system to destroy tumors.

## Key facts

- **NIH application ID:** 9992888
- **Project number:** 1F31CA250488-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Victoria Huannyun Wu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,401
- **Award type:** 1
- **Project period:** 2020-08-26 → 2021-08-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992888

## Citation

> US National Institutes of Health, RePORTER application 9992888, Targeting the Immune Onco-GPCRome  as a Novel Multimodal Cancer Immunotherapy Strategy (1F31CA250488-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9992888. Licensed CC0.

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