Related Experiment Video

Updated: Dec 12, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

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Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors

Qingyang Lei1,2,3, Dan Wang1,2,3, Kai Sun4

  • 1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Frontiers in Cell and Developmental Biology
|August 15, 2020
PubMed

Insights

Immune checkpoint inhibitors targeting PD1/PDL1 are effective but limited by resistance. Understanding resistance mechanisms is key to improving cancer immunotherapy efficacy for more patients.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • The programmed cell death protein 1 (PD1) and its ligand PDL1 pathway is crucial in tumor immune evasion.
  • Anti-PD1/PDL1 immunotherapy has shown success but faces significant primary and acquired resistance.
  • Identifying resistance mechanisms is critical to enhance patient response rates and durability.

Purpose of the Study:

  • To explore the detailed mechanisms underlying primary and acquired resistance to anti-PD1/PDL1 therapy.
  • To review biomarkers for predicting patient response to PD1/PDL1 blockade.
  • To discuss potential strategies for overcoming anti-PD1/PDL1 resistance in cancer treatment.

Main Methods:

  • Review of current literature on PD1/PDL1 resistance mechanisms.
  • Analysis of identified biomarkers associated with immunotherapy response.
  • Exploration of therapeutic strategies to overcome resistance.

Main Results:

  • Primary resistance mechanisms include low tumor immunogenicity, MHC dysfunction, T cell exhaustion, and an immunosuppressive microenvironment.
  • Acquired resistance involves tumor immunoediting, compensatory signaling, and T cell re-exhaustion.
  • Biomarkers for predicting response and strategies to overcome resistance are being investigated.

Conclusions:

  • Resistance to PD1/PDL1 blockade is multifactorial, involving tumor-intrinsic and extrinsic factors.
  • Further research into resistance mechanisms and predictive biomarkers is essential for optimizing immunotherapy.
  • Developing novel strategies to overcome resistance will expand the clinical benefit of PD1/PDL1-targeted therapies.
Keywords:
PD1PDL1cancerimmunotherapymechanismresistance

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