Yang Qi-Chao, Sun Heng, Sun Zhi-Jun
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China.
Biochem Pharmacol. 2025 Sep;239:117043. doi: 10.1016/j.bcp.2025.117043. Epub 2025 Jun 6.
Cancer immunotherapy has changed the therapeutic landscape for multiple types of cancer, yet a majority of patients do not respond or develop resistance. Dysregulated activation of oncogenic signalling pathways can lead to tumour immune evasion and the creation of an immunosuppressive "cold" tumour microenvironment, contributing to resistance to immunotherapy. Research indicates that targeting these oncogenic pathways can enhance antitumour immune responses and convert "cold" tumours into "hot" ones, thereby improving the efficacy of immunotherapy. This review summarizes the recent advance of oncogenic signalling on tumour immune evasion and the formation of a "cold" tumour microenvironment. It also summarizes the mechanisms by which targeting oncogenic signalling pathways to enhance antitumour immunity and its effects on cancer immunotherapy. Additionally, therapeutic targets and agents for oncogenic signalling pathways, along with drug-target structural binding mechanisms, are summarized in this study. Relevant clinical trials involving the combination of oncogenic pathway inhibitor and cancer immunotherapy are reviewed. Finally, we discuss the current status and challenges of targeting oncogenic signalling pathways to enhance immunotherapy and outlined potential future research directions based on current findings.
癌症免疫疗法已经改变了多种癌症的治疗格局，然而大多数患者没有反应或产生耐药性。致癌信号通路的失调激活可导致肿瘤免疫逃逸，并形成免疫抑制性的“冷”肿瘤微环境，从而导致对免疫疗法产生耐药性。研究表明，靶向这些致癌通路可以增强抗肿瘤免疫反应，并将“冷”肿瘤转化为“热”肿瘤，从而提高免疫疗法的疗效。本综述总结了致癌信号在肿瘤免疫逃逸和“冷”肿瘤微环境形成方面的最新进展。它还总结了通过靶向致癌信号通路增强抗肿瘤免疫力的机制及其对癌症免疫疗法的影响。此外，本研究总结了致癌信号通路的治疗靶点和药物，以及药物-靶点结构结合机制。综述了涉及致癌通路抑制剂与癌症免疫疗法联合应用的相关临床试验。最后，我们讨论了靶向致癌信号通路增强免疫疗法的现状和挑战，并根据当前研究结果概述了潜在的未来研究方向。
