[Primary resistance mechanisms of immune checkpoint inhibitors in cancer].

In recent years, immune checkpoint inhibitor (ICI) therapy has achieved a breakthrough in cancer treatment. By targeting and blocking immune checkpoint molecules on T cells, ICIs release inhibited anti-tumor immune responses, demonstrating durable clinical efficacy and improved long-term survival across multiple cancer types. However, only a minority of cancer patients currently benefit from ICI treatment, with primary resistance observed in most malignancies. Clarifying the mechanisms underlying primary resistance to ICI therapy is conducive to the development of effective combination strategies for overcoming drug resistance. This review systematically examines the molecular basis of primary resistance to ICIs through following aspects: tumor lymphocyte infiltration phenotype, interferon signaling pathways, antigen presentation machinery, and tumor cell-intrinsic oncogenic signaling pathways, which may provide novel therapeutic targets and rational combination strategies for cancer immunotherapy.