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Related Experiment Video

Updated: Jan 29, 2026

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

Published on: March 28, 2025

Targeting PIM2 improves antitumor immunity through promoting effector function and persistence of CD8 T cells.

Yongxia Wu^1,2, Linlu Tian¹, Allison Pugel¹

¹Department of Microbiology & Immunology and.

The Journal of Clinical Investigation

|January 27, 2026

Summary

PIM2 kinase suppresses anti-tumor immunity by impairing CD8 T cell function. Inhibiting PIM2 enhances T cell responses, offering a promising strategy for cancer immunotherapy.

Keywords:

Cell biology Cellular immune response Immunology Immunotherapy T cells

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Area of Science:

Immunology
Oncology
Molecular Biology

Background:

The PIM kinase family plays a role in tumorigenesis.
PIM2's function in primary T cells and anti-tumor immunity is understudied.
PIM2 is distinct from other isoforms and inhibits T-cell responses.

Purpose of the Study:

To investigate the role of PIM2 as a regulator of anti-tumor immunity.
To elucidate the mechanisms by which PIM2 affects T cell function.
To evaluate PIM2 inhibition as a therapeutic strategy in cancer immunotherapy.

Main Methods:

Utilized murine cancer models (breast cancer, melanoma, leukemia) with Pim2-deficient T cells.
Analyzed cytokine production, metabolic activity, TCF1 expression, and memory phenotype in CD8 T cells.
Investigated PIM2's role in autophagy, glycolysis, and EZH2 activity.
Tested PIM2 inhibitor JP11646 in murine models and engineered human T cells (TCR-T, CAR-T).

Main Results:

Pim2 deficiency enhanced T cell-mediated tumor control and effector functions.
Pim2 deficiency promoted a memory-like phenotype in CD8 T cells.
PIM2 impairs T cell anti-tumor immunity by inhibiting autophagy and glycolysis.
PIM2 inhibition of EZH2 activity disrupts CD8 T cell memory.
PIM2 inhibition with JP11646 enhanced anti-tumor T cell responses in mice and humans.

Conclusions:

PIM2 is a key negative regulator of anti-tumor immunity.
Targeting PIM2 enhances effector differentiation and persistence of CD8 T cells.
PIM2 inhibition is a promising strategy for improving cancer immunotherapy.