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N-cadherin inhibitor creates a microenvironment that protect TILs from immune checkpoints and Treg cells

Yi Sun1,2, Jun Jing3,4, Huan Xu2,5

  • 1Department of Urology, West China Hospital of Sichuan University, Chengdu, China.

Journal for Immunotherapy of Cancer
|March 11, 2021
PubMed
Abstract

Insights

N-cadherin promotes tumor immune evasion by upregulating PD-L1 and IDO-1. The N-cadherin antagonist ADH-1 reverses this, enhancing tumor-infiltrating lymphocyte (TIL) therapy for prostate cancer.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Current immunotherapies offer limited benefit to prostate cancer patients.
  • Novel strategies are needed to improve immunotherapy efficacy in prostate cancer.

Purpose of the Study:

  • To investigate the role of N-cadherin in prostate cancer immune evasion.
  • To evaluate the therapeutic potential of an N-cadherin antagonist (ADH-1) in combination with tumor-infiltrating lymphocyte (TIL) therapy.

Main Methods:

  • Utilized human tissues, cell lines, and in vivo models (hNSG mice) to assess N-cadherin's impact on PD-L1, IDO-1, and effector Treg cell production.
  • Administered ADH-1 to PC3-bearing hNSG mice treated with TILs to evaluate therapeutic efficacy.

Main Results:

  • N-cadherin significantly increased PD-L1 and IDO-1 expression via IFN-γ signaling, promoting immunosuppressive eTreg cells.
  • TIL therapy initially slowed tumor growth but was negated by PD-L1, IDO-1, and eTreg-mediated immune suppression.
  • ADH-1 treatment effectively reduced immunosuppression and augmented the anti-tumor effects of TIL therapy.

Conclusions:

  • N-cadherin antagonist ADH-1 enhances TIL-mediated anti-tumor responses in prostate cancer.
  • Targeting N-cadherin represents a promising strategy to overcome immune suppression and improve immunotherapy outcomes.
Keywords:
immune reconstitutionprostatic neoplasms

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