Although immunotherapy is now established as the newest pillar of cancer treatment, a basic question concerning how immune checkpoint inhibition works has yet to be addressed: “Where do the T cells that kill the tumor come from, and what do they look like?” In late 2017, we began to apply both CyTOF and single-cell sequencing technologies to solid tumors to define the immune expression of TIGIT family receptors. Identifying the T cells that drive immunotherapy response was not the initial goal, but our comprehensive analyses of tumor-infiltrating immune cells led us to focus on this question.