# Elucidating The Roles of PIK3IP1/TrIP Regulation on Distinct T Cell Subsets in the Context of Cancer

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $22,626

## Abstract

PROJECT SUMMARY
The signaling pathways involving phosphoinositide-3-kinases (PI3Ks) are highly conserved and tightly regulated
to influence the activation, proliferation, and survival of all cell types. PI3K signaling plays a major role in T cell
responses to antigen due to its position directly downstream of T cell receptor (TCR)/CD28 ligation. Our lab has
recently shown that the cell surface protein TrIP (Transmembrane Inhibitor of PI3K, gene name: Pik3ip1) has a
distinctly high expression on T cells and is capable of downregulating PI3K signaling in CD4+ T cells, acting as
a negative regulator of T cell immune responses. These studies revealed that CD4+ T cells lacking TrIP
expression exhibit a more Th1 inflammatory phenotype compared to WT controls both in vivo and in vitro. These
data have led us to propose that TrIP restricts the inflammatory activity of CD8+ T cells, and that
targeting/knockout of this negative regulator may promote anti-tumor immunity. I have already obtained
preliminary data demonstrating that CD8+ T cell-specific TrIP knockout mice (TrIPfl/flE8icre) are resistant to growth
of syngeneic tumors. In addition to increased tumor resistance, we have also found that tumors harvested from
our TrIPfl/flE8icre knockout mice contain twice as many infiltrating T cells compared to their WT counterparts. We
also found that CD8+ T cells were the main drivers of this increased T cell infiltration, as their frequency was
double that of the CD4+ population. These preliminary data are the basis of our proposal aimed at further
elucidating cell-intrinsic effects of TrIP activity in CD8+ T cells, including its impact on antitumor immunity. These
studies will not only improve our understanding of TrIP as a negative immune regulator, but also inform on the
potential for TrIP as a future immunotherapeutic target.

## Key facts

- **NIH application ID:** 10772152
- **Project number:** 5F31CA261039-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Benjamin Murter
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $22,626
- **Award type:** 5
- **Project period:** 2022-02-01 → 2024-05-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10772152

## Citation

> US National Institutes of Health, RePORTER application 10772152, Elucidating The Roles of PIK3IP1/TrIP Regulation on Distinct T Cell Subsets in the Context of Cancer (5F31CA261039-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10772152. Licensed CC0.

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