Biomarkers for Cancer Immunotherapy: Advances, Challenges, and Clinical Applications

Cancer immunotherapy has revolutionized oncology by harnessing the immune system to recognize and eliminate malignant cells. Despite remarkable clinical successes, a substantial proportion of patients fail to respond or develop resistance, highlighting the urgent need for reliable biomarkers to guide patient selection, predict therapeutic outcomes, and monitor treatment responses. This review addresses both the emerging and established biomarkers for cancer immunotherapy. These include molecular, cellular, and systemic biomarkers within tumor tissues, blood, and the tumor microenvironment. The principal ones include immune checkpoint-related biomarkers (e.g., programmed death-ligand 1 (PD-L1) expression), tumor mutational burden, microsatellite instability, neoantigen profiling, circulating tumor DNA, and immune cell signatures. We grade each biomarker by analytical validity, clinical validity, clinical utility and regulatory readiness; place it in one of four evidence tiers; and outline the steps needed to bring candidate markers into the clinic. Recent developments in multi-omics technologies, artificial intelligence, and single-cell analysis are accelerating biomarker discovery, providing a clearer understanding of tumor–immune interactions. Furthermore, the integration of dynamic biomarkers is critical for optimally refining therapeutic strategies for real-time monitoring and detection of resistance mechanisms. This review aims to provide a worldwide overview of present achievements, challenges, and future opportunities in biomarker research and ultimately enable the development of more personalized and effective strategies for immunotherapy of cancer.