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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

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Pik3ip1/TrIP Regulation of PI3K Restricts CD8 T Cell Anti-Tumor Immunity.

Benjamin M Murter¹, Lawrence P Kane¹

¹Department of Immunology, Graduate Program in Microbiology and Immunology, University of Pittsburgh, Pittsburgh, PA 15213.

Biorxiv : the Preprint Server for Biology

|August 12, 2025

Summary

Transmembrane inhibitor of PI3K (TrIP) restricts CD8 T cell anti-tumor immunity. Removing TrIP enhances T cell responses, reduces tumor growth, and may offer novel cancer therapy distinct from current checkpoint inhibitors.

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Area of Science:

Immunology
Cancer Biology
Molecular Biology

Background:

PI3K-interacting protein (PIK3IP1), also known as transmembrane inhibitor of PI3K (TrIP), is expressed in T cells and modulates PI3K activity.
TrIP is downregulated upon T cell activation and influences T cell differentiation.

Purpose of the Study:

To investigate the role of TrIP in CD8 T cell-mediated anti-tumor immunity.
To determine if TrIP deficiency impacts tumor growth and T cell responses in vivo.

Main Methods:

Generated CD8-specific TrIP knockout (KO) mice.
Implanted mice with B16 melanoma or MC38 colon carcinoma tumors.
Analyzed tumor growth, anti-tumor immunity, and transcriptional profiles of CD8 T cells.

Main Results:

TrIP KO CD8 T cells exhibited an enhanced inflammatory transcriptional profile.
CD8-specific TrIP deficiency led to reduced tumor growth and increased tumor-infiltrating T cells.
TrIP deficiency delayed T cell exhaustion and increased the diversity of T cell responses to tumor neoantigens.

Conclusions:

TrIP intrinsically restricts the CD8 T cell response against tumors.
Targeting TrIP could augment anti-tumor immunity through mechanisms distinct from current checkpoint therapies.