The identity and frequency of immune cells in the tumor microenvironment impact outcomes for patients with colorectal cancer. Using single-cell RNA sequencing data, Foroutan et al. identify signatures of residency and exhaustion for tumor-infiltrating CD8⁺, CD4⁺, and natural killer (NK) cells. Different signature combinations associated with distinct patient outcomes; for example, signatures of high NK-cell exhaustion and low NK-cell residency were associated with improved survival. The data provide new insight into the characteristics of tumor-infiltrating lymphocytes and suggest that preventing tumor residency by NK cells may enhance antitumor immunity and patient outcomes. Read more in this issue on page 1125. Artwork by Momeneh Foroutan inspired by several figures in the article, including the CD8 residency panel of Fig. 1B, shown here.