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September 28, 2025Molecular Cancer Therapeutics

Inhibiting arginine metabolism via ALDH2/ARG2 axis blockade potentiates immune checkpoint inhibitors in colorectal cancer

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Authors

LCLu CaiUniversity of LouisvilleYCY Z CaoJZJiawei ZhangSouthern University of Science and Technology

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Overview

This research reveals ALDH2's role in immunotherapy resistance in CRC, suggesting ARG2 as a target for enhancing immune checkpoint blockade.

Key Points

  • Combinatorial blockade of ARG2 with immune checkpoint inhibitors significantly restores anti-tumor immunity in colorectal cancer.
  • High levels of ALDH2 correlate with reduced extracellular L-arginine availability, which compromises CD8+ T cell functions.
  • ALDH2 upregulates transcription of ARG2, leading to decreased glycolysis and suppressed proliferation of CD8+ T cells.
  • Metabolomic profiling identifies ALDH2 as a key regulator in L-arginine metabolism, affecting immunotherapy responses.

Cite This Study

Cai et al. (2025) studied this question.

synapsesocial.com/papers/68d909fc41e1c178a14f5b3dhttps://doi.org/10.1158/1535-7163.mct-25-0404
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