Related Experiment Video

Updated: Sep 8, 2025

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
09:04

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

Published on: March 7, 2025

661

Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

Tae Kon Kim1,2, Esten N Vandsemb3, Roy S Herbst2

  • 1Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Nature Reviews. Drug Discovery
|June 14, 2022
PubMed

Insights

Tumours develop adaptive immune resistance (AIR) to evade immune attack. Understanding these AIR mechanisms is crucial for developing effective cancer therapies beyond current anti-PD treatments.

Area of Science:

  • Immunology
  • Cancer Biology
  • Drug Development

Background:

  • Tumours evade immune responses through adaptive immune resistance (AIR) mechanisms.
  • Programmed cell death 1 ligand 1 (PDL1) induction by interferon-γ is a validated AIR mechanism.
  • Anti-PD therapy shows efficacy in a subset of advanced cancers, particularly solid tumours.

Purpose of the Study:

  • To highlight the importance of defining AIR mechanisms at the tumour site.
  • To guide future drug development strategies for cancer therapy.
  • To propose practical approaches for enhancing current cancer treatments.

Main Methods:

  • Review of existing literature on adaptive immune resistance.
  • Analysis of clinical trial outcomes combining anti-PD therapy with other drugs.
  • Discussion of mechanistic rationale for drug development.

Main Results:

  • Many combination therapies fail due to a lack of mechanistic understanding.
  • Defining specific AIR mechanisms is key to improving therapeutic outcomes.
  • Targeting AIR offers potential for synergistic or additive effects.

Conclusions:

  • A deeper understanding of tumour-specific AIR mechanisms is essential.
  • Future cancer drug development should focus on rational combination strategies.
  • Optimizing current anti-PD therapy requires a focus on overcoming resistance.

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