Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by harnessing the immune system to target tumors, leading to durable responses in various malignancies. However, the efficacy of ICIs varies widely among patients, necessitating a deeper understanding of pharmacogenomics to optimize therapeutic outcomes.This abstract provides an overview of the cellular responses to ICIs and explores pharmacogenomic strategies aimed at enhancing treatment efficacy and overcoming resistance mechanisms.

ICIs function by blocking inhibitory pathways, such as CTLA-4, PD-1, and PD-L1, thereby unleashing T-cellmediated anti-tumor immune responses. Variability in treatment response is influenced by genetic factors, including polymorphisms in immune checkpoint genes and tumor mutational burden (TMB), which affect immune recognition and response to therapy. Additionally, the gut microbiome composition and host immune profile play crucial roles in modulating treatment outcomes by influencing systemic immune activation and tumor microenvironment dynamics.

Pharmacogenomic approaches to optimize ICI therapy include biomarker identification, such as PD-L1 expression and TMB, to stratify patients likely to benefit from treatment. Combination therapies with other immunomodulators or targeted agents aim to synergize immune responses and overcome resistance mechanisms. Genomic profiling and AI-driven analyses enable personalized treatment strategies based on individual patient
characteristics and tumor biology.