Peripheral blood biomarkers for predicting response to PD-1/PD-L1 inhibitors

Though programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors have revolutionized cancer treatment, predicting their therapeutic efficacy largely depends on biomarkers obtained through invasive procedures, which present challenges, particularly for continuous sampling. Compared to tumor-based biomarkers, peripheral blood biomarkers offer distinct advantages, including non-invasive accessibility and the potential for dynamic monitoring. Although numerous studies suggest that peripheral blood biomarkers hold significant value, the lack of consensus on indicators and standards underscores the necessity of integrating evidence to guide future research. This review synthesizes cutting-edge peripheral blood testing achievements for predicting PD-1/PD-L1 immunotherapy response, encompassing tumor-derived biomarkers (circulating tumor cell, circulating tumor DNA, blood tumor mutation burden, etc.), multidimensional immune profiling (lymphocyte count, neutrophil-to-lymphocyte ratio, T/B/NK/myeloid subsets, cytokines), and multi-parameter models. We collectively validate the reliability of peripheral blood biomarkers and identify high-potential candidates that could be further developed through computationally-driven frameworks and multi-center cohorts in the future.