Contrary to the classical view of immunologically “hot” vs. “cold” tumors defined by the mere presence or absence of T cell infiltration, we and others found that anti-PD-1 (aPD-1) checkpoint blockade induced clonal replacement of T cells, subsequent expansion detectable in the peripheral blood, migration into the tumor, followed by multiple rounds of activation, expansion, and ultimately T cell exhaustion (7, 8). Here, PDCD1 is linked to neoplasm.