Tumour- and Non-Tumour-Associated Factors That Modulate Response to PD-1/PD-L1 Inhibitors in Non-Small Cell Lung...

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Immune checkpoint inhibitors targeting PD-1/PD-L1 pathways offer therapeutic benefits in cancer, particularly non-small cell lung cancer (NSCLC).
• Current patient selection relies on PD-L1 tumour proportion score (TPS), but its imperfect predictive accuracy limits treatment efficacy for many advanced NSCLC patients.
• Tumour immune evasion mediated by PD-1/PD-L1 interactions necessitates the identification of novel predictive biomarkers.

Purpose of the Study:

• To review tumour- and non-tumour-associated factors influencing response to PD-1/PD-L1 inhibitors in NSCLC.
• To explore mechanistic and clinical evidence for potential biomarkers beyond PD-L1 TPS.
• To investigate the role of these biomarkers in relation to the tumour microenvironment (TME).

Main Methods:

• Literature review of studies investigating biomarkers for PD-1/PD-L1 inhibitor response in NSCLC.
• Analysis of mechanistic data on tumour- and non-tumour-associated factors.
• Examination of clinical evidence supporting the utility of novel biomarkers.

Main Results:

• PD-L1 TPS is an imperfect biomarker for predicting response to PD-1/PD-L1 blockade therapy in NSCLC.
• Numerous tumour- and non-tumour-associated factors, beyond PD-L1 expression, impact immunotherapy outcomes.
• These factors are intricately linked to the tumour microenvironment (TME) and offer potential for improved patient stratification.

Conclusions:

• Additional biomarkers are crucial for optimizing patient selection for PD-1/PD-L1 inhibitor therapy in NSCLC.
• Understanding diverse predictive markers and their TME interactions can enhance immunotherapy efficacy.
• Further research into these novel biomarkers is warranted to improve treatment outcomes for NSCLC patients.