====== T cell cytotoxicity ======
[[Immunotherapy]] has transformed [[cancer treatment]]s; however, a large fraction of [[patient]]s encounter [[resistance]]. Such resistance is mediated by complex factors, often involving interactions between multiple [[gene]]s. Thus, it is crucially important to identify genetic interactions between genes that are significantly mutated in cancer patients and those involved in [[immune response]]s, ideally the ones that currently have chemical compounds for direct targeting. To systematically interrogate such genetic interactions that mediate cancer cells' response to [[T cell]] killing, Park et al. designed an asymmetric dual perturbation [[library]] targeting the matched combinations between significantly mutated [[tumor suppressor]]s and immune resistance genes. They performed a combinatorial double [[knockout]] screen on 1159 gene pairs and identified those where joint loss-of-function renders altered cellular response to [[T cell]] [[cytotoxicity]]. They also performed comparative [[transcriptomics]]-based analyses on tumor and normal samples from [[TCGA]] and [[Genotype-Tissue Expression]] cohorts, [[mutation]]al profiling analyses, and [[survival analysis]] to further characterize the significance of identified hits in clinical patients. Interactions between significantly mutated [[tumor suppressor]]s and potentially druggable [[immune resistance]] genes may offer insights on potential new concepts of how to target clinically relevant cancer mutations with currently available agents
((Park JJ, Codina A, Ye L, Lam S, Guo J, Clark P, Zhou X, Peng L, Chen S. Double knockout CRISPR screen for cancer resistance to T cell [[cytotoxicity]]. J Hematol Oncol. 2022 Dec 1;15(1):172. doi: 10.1186/s13045-022-01389-y. PMID: 36456981.))