Cancer clones that escape immune recognition can hijack CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1 (programmed cell death protein 1) checkpoint blockade, resulting in heterogeneous tumors with a complex immunogenomic profile which may include immune exhaustion, giving rise to mixed or unfavorable response to immune checkpoint inhibition1,3. The gene discussed is PDCD1; the disease is cancer.