KLRG1 not only marks the majority of circulating cytotoxic tumor-TCR-matched CD4+ T cells, serving as a biomarker to monitor these cells as a window into intratumoral CD4+ T cell recognition, but also separately regulates their killing activity through its cognate interaction with tumor E-cadherin, as an inhibitory gate that operates independently of PD-1. This evidence concerns the gene PDCD1 and neoplasm.