'Know thyself' - host factors influencing cancer response to immune checkpoint inhibitors

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but show unpredictable patient responses.
• Current FDA-approved biomarkers for ICI therapy require tumor tissue, limiting broader application.
• Host factors, including genetic, metabolic, immune, and gut microbiota profiles, are emerging as critical determinants of ICI response.

Purpose of the Study:

• To review key host factors with potential as predictive biomarkers for ICI therapy response.
• To explore the proposed mechanisms by which these host factors influence treatment outcomes.
• To highlight modifiable host factors that could be targeted for combination therapies.

Main Methods:

• Literature review of studies investigating host factors and ICI response.
• Analysis of proposed biological mechanisms linking host factors to immune response.
• Synthesis of evidence for biomarker potential and therapeutic implications.

Main Results:

• Host factors such as genetic predispositions, metabolic status, immune cell profiles, and gut microbiome composition significantly impact ICI efficacy.
• These factors offer potential as non-tumor-based biomarkers for predicting treatment response.
• Some identified host factors are amenable to modification, suggesting opportunities for novel therapeutic strategies.

Conclusions:

• Host factors represent a promising area for developing novel predictive biomarkers for immune checkpoint inhibitor therapy.
• Understanding these factors can guide the development of co-therapies to improve treatment outcomes in oncology.
• Further research into host-directed biomarkers and interventions is warranted to personalize cancer immunotherapy.