Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Programmed cell death protein-1/programmed death-ligand 1 (PD-(L)1) axis inhibitors represent a major advance in cancer treatment.
• However, primary and acquired resistance to PD-(L)1 therapies significantly limits their clinical efficacy in many patients.

Purpose of the Study:

• This review synthesizes current understanding of resistance mechanisms to PD-(L)1 therapies.
• It also examines the current landscape and future challenges in developing predictive biomarkers for these immunotherapies.

Main Methods:

• Literature review of studies on PD-(L)1 resistance mechanisms.
• Analysis of current biomarker development strategies for PD-(L)1 inhibitors.
• Discussion of challenges in patient selection for immunotherapy.

Main Results:

• Multiple mechanisms contribute to primary and acquired resistance to PD-(L)1 blockade.
• Existing biomarkers have limitations in predicting response to PD-(L)1 therapies.
• Significant challenges exist in developing and validating novel biomarkers.

Conclusions:

• Overcoming resistance to PD-(L)1 therapies requires a deeper understanding of underlying biological mechanisms.
• Innovation in biomarker development and patient selection strategies is essential.
• Accelerating the delivery of effective immunotherapy to responsive patients necessitates novel approaches.