Therefore, in contrast to its tumor-promoting function in the context of immunity, cancer cell-intrinsic PD-1/PD-L1 works actually as a tumor suppressor (Du et al., 2018; Wang et al., 2020b; Ieranò et al., 2022), a finding that complicates cancer therapy using PD-1/PD-L1 blockade and the outcomes of patients in response to therapy. The gene discussed is PDCD1; the disease is neoplasm.