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Related Experiment Video

Updated: Jul 8, 2025

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

Re-"Formate" T-cell Antitumor Responses.

Mei-Chun Lin^1,2,3, Sofie Hedlund Moller^1,3, Ping-Chih Ho^1,3

¹Department of Oncology, University of Lausanne, Lausanne, Switzerland.

Cancer Discovery

|December 12, 2023

Summary

T-cell activation rewires one-carbon metabolism to support immune responses. Supplementing with formate rescues dysfunctional T cells, enhancing anti-PD-1 therapy effectiveness in tumors.

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Area of Science:

Immunology
Metabolic pathways
Cancer immunotherapy

Background:

T-cell activation requires metabolic support for proliferation and effector functions.
The tumor microenvironment can impose metabolic constraints on anti-tumor immune cells.
Immune checkpoint blockade, like anti-PD-1, relies on functional T cells.

Purpose of the Study:

To investigate metabolic rewiring in CD8+ T cells during activation.
To determine if one-carbon metabolism supports T-cell proliferation and cytolytic activity.
To evaluate formate supplementation as a strategy to enhance anti-PD-1 therapy.

Main Methods:

Analysis of one-carbon metabolism in activated CD8+ T cells.
Assessment of T-cell proliferation and cytolytic activity.
In vivo studies involving formate supplementation and anti-PD-1 treatment in tumor models.

Main Results:

T-cell activation triggers significant rewiring of one-carbon metabolism.
Formate supplementation rescued dysfunctional T cells and restored their responsiveness.
Enhanced anti-PD-1 efficacy was observed in specific tumor-infiltrated T-cell subsets with formate support.

Conclusions:

One-carbon metabolism is critical for CD8+ T-cell function post-activation.
Targeting metabolic vulnerabilities in the tumor microenvironment can improve immunotherapy.
Formate supplementation is a promising strategy to boost anti-PD-1 therapy.