Fig. 15

Identifying cancer-immunity cycle regulators through CRISPR screens. The cancer-immunity cycle outlines the step-by-step development of immune responses against tumors. CRISPR screening can be employed to examine cells at each stage of this cycle, identifying regulatory genes and the resulting phenotypic effects. A In the initial phase, tumor antigens are released by cancer cells and collected by APCs such as DCs, which may secrete cytokines when stimulated. APCs process and present the captured antigens using major histocompatibility complex proteins on their surface. APC trafficking to nearby lymph nodes enables cancer antigen presentation to naïve T cells, leading to T cell activation. Screens on APCs can reveal genes that regulate APC stimulation in response to tumor antigens and antigen presentation efficiency to T cells. B T cells exposed to antigens become primed and activated to target specific tumor antigens. T cell screens can pinpoint genes responsible for activation efficiency. C Primed T cells, including cytotoxic T lymphocytes, exit the lymph node, travel through the bloodstream, and infiltrate tumors as tumor-infiltrating lymphocytes (TILs). In vivo T cell screens can identify genes that facilitate TIL trafficking and infiltration. D Inside the tumor, T cells can finally recognize and respond to cancer-specific antigens, leading to tumor cell destruction. T cell screens can detect genes that improve tumor-killing activity. E Concurrently, screening tumor cells can uncover genes involved in resistance to T cell killing. CRISPR screens can identify positive regulators (shown in red) and negative regulators (shown in blue) at each step of the process. Reprinted from [657] with permission from Springer Nature