| Summary: | Abstract Recent breakthroughs in targeted therapy and immunotherapy have revolutionized the treatment of lung cancer, the leading cause of cancer-related deaths in the United States and worldwide. Here we provide an overview of recent progress in immune checkpoint blockade therapy for treatment of non-small cell lung cancer (NSCLC), and discuss biomarkers associated with the treatment responses, mechanisms underlying resistance and strategies to overcome resistance. The success of immune checkpoint blockade therapies is driven by immunogenicity of tumor cells, which is associated with mutation burden and neoantigen burden in cancers. Lymphocyte infiltration in cancer tissues and interferon-γ–induced PD-L1 expression in tumor microenvironments may serve as surrogate biomarkers for adaptive immune resistance and likelihood of responses to immune checkpoint blockade therapy. In contrast, weak immunogenicity of, and/or impaired antigen presentation in, tumor cells are primary causes of resistance to these therapies. Thus, approaches that increase immunogenicity of cancer cells and/or enhance immune cell recruitment to cancer sites will likely overcome resistance to immunotherapy.
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