Du Yi, Yang Yang, Zheng Bohao, Zhang Qian, Zhou Shengtao, Zhao Linjie
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Oncogene. 2025 Mar;44(7):409-426. doi: 10.1038/s41388-025-03273-8. Epub 2025 Jan 25.
Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle in a haystack at the genetic level. In cancer research, gene mutations are closely related to tumor development, metastasis, and recurrence, and the use of state-of-the-art powerful screening technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), to search for the most critical genes or coding products provides us with a new possibility to further refine the cancer mapping and provide new possibilities for the treatment of cancer patients. The use of CRISPR screening for the most critical genes or coding products has further refined the cancer atlas and provided new possibilities for the treatment of cancer patients. Immunotherapy, as a highly promising cancer treatment method, has been widely validated in the clinic, but it could only meet the needs of a small proportion of cancer patients. Finding new immunotherapy targets is the key to the future of tumor immunotherapy. Here, we revisit the application of functional screening in cancer immunology from different perspectives, from the selection of diverse in vitro and in vivo screening models to the screening of potential immune checkpoints and potentiating genes for CAR-T cells. The data will offer fresh therapeutic clues for cancer patients.
全基因组功能遗传筛选已在生物医学领域广泛应用，这使得在基因层面大海捞针成为可能。在癌症研究中，基因突变与肿瘤的发生、转移和复发密切相关，利用诸如成簇规律间隔短回文重复序列（CRISPR）等先进的强大筛选技术来寻找最关键的基因或编码产物，为我们进一步完善癌症图谱以及为癌症患者的治疗提供了新的可能性。使用CRISPR筛选最关键的基因或编码产物进一步完善了癌症图谱，并为癌症患者的治疗提供了新的可能性。免疫疗法作为一种极具前景的癌症治疗方法，已在临床上得到广泛验证，但它仅能满足一小部分癌症患者的需求。寻找新的免疫治疗靶点是肿瘤免疫治疗未来发展的关键。在此，我们从不同角度重新审视功能筛选在癌症免疫学中的应用，从多种体外和体内筛选模型的选择到潜在免疫检查点以及CAR-T细胞增强基因的筛选。这些数据将为癌症患者提供新的治疗线索。
