Critical factors of primary response resistance to immune checkpoint blockade have been increasingly recognized, including tumor-intrinsic factors (tumor neoantigen burden and activation of oncogenic signaling pathways), TME (low tumor-infiltrating lymphocytes, exhausted CD8+ T cells, immunosuppressive cells and epigenetic silencing of chemokine), host immune components and microbiomes. The gene discussed is CD8A; the disease is neoplasm.