冷冻消融联合免疫检查点抑制剂的协同机制与临床前景综述
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v7i5.16546
Abstract
冷冻消融作为一种有效的局部肿瘤治疗技术,因其能够重塑肿瘤免疫微环境(TME)而引起广泛关注。肿瘤免疫微环境的复杂性和免疫抑制状态是当前肿瘤免疫治疗面临的主要障碍。近年来,免疫检查点抑制剂(ICI)的应用显著改善了多种肿瘤的治疗效果,但其疗效受限于免疫微环境的抑制性特点。基于此,本文综述了冷冻消融在促进肿瘤抗原释放、激活免疫效应细胞及调节免疫抑制因子方面的作用机制,重点分析其与ICI联合应用的协同效应及潜在临床优势。通过整合最新基础研究和临床前试验数据,探讨了该联合策略在增强免疫反应、逆转免疫耐受方面的潜力,同时剖析了当前面临的技术挑战和未来研究方向。该综述旨在为冷冻消融联合免疫治疗的临床转化提供理论依据和实践指导,推动肿瘤治疗新策略的发展,未来研究需致力于优化联合治疗时序与剂量,并探索预测性生物标志物,以加速其临床转化与应用。
Keywords
冷冻消融；肿瘤免疫微环境；肿瘤免疫联合治疗；免疫检查点抑制剂；协同机制；临床前景
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[7] Taqi K,Stockley C,Wood M,Przybojewski S, Bouchard-For tier A, Mack L. Cryotherapy in the Treatment of Extra-Abdomi nal Desmoid Tumors-A Review[J].Curr Oncol,2025,32(3).
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[37] Lu D,Gao Y.Immune Checkpoint Inhibitor-related Endo crinopathies[J].J Transl Int Med,2022,10(1):9-14.
[38] Su Q,Zhao L,Banfield JM,et al.Immune-Related Adverse Event of Immunotherapy: Diabetes[J].Clin Lab,2025,71(3).
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[41] Raikhelkar J, Uriel N.Immune checkpoint inhibitor myocarditis[J].Curr Opin Cardiol,2019,34(3):303-306.
[42] Zhang L,Jones-O’Connor M, Awadalla M,et al.Cardioto xicity of Immune Checkpoint Inhibitors[J]. Curr Treat Options Cardiovasc Med,2019,21(7):32.
[43] Jo W, Won T, Daoud A, Čiháková D. Immune checkpoint inhibitors associated cardiovascular immune-related adverse events[J].Front Immunol,2024,15:1340373.
[44] Herrmann SM,Perazella MA.Immune Checkpoint Inhibit ors and Immune-Related Adverse Renal Events[J]. Kidney Int Rep,2020,5(8):1139-1148.
[45] Lui RN,Leung LKS,Chan SL.Immune Checkpoint Inhibit or-induced Enterocolitis[J].Clin Gastroenterol Hepatol, 2021, 19(7):e70.
[46] Plaçais L,Lambotte O.Long-term immune related adve rse events[J].Curr Opin Oncol,2025,37(2):142-149.
[47] Zhang Z,Li D,Yun H,et al. CAR-T Cells in the Treatment of Urologic Neoplasms:Present and Future[J].Front Oncol,2022, 12:915171.
[48] Hori J, Kunishige T,Nakano Y.Immune Checkpoints Cont ribute Corneal Immune Privilege: Implications for Dry Eye Associated with Checkpoint Inhibitors[J]. Int J Mol Sci, 2020, 21(11).
[49] Princk MH, Pervan M,Riedl J.[Management of immunerelated adverse events][J].Urologie,2025,64(3):281-287.
[50] Ramos-Casals M,Sisó-Almirall A.Immune-Related Adve rse Events of Immune Checkpoint Inhibitors[J]. Ann Intern Med, 2024,177(2):ITC17-ITC32.
[51] Aarts BM,Klompenhouwer EG,Rice SL,et al.Cryoablation and immunotherapy: an overview of evidence on its synergy[J]. Insights Imaging,2019,10(1):53.
[52] Yakkala C, Denys A, Kandalaft L, Duran R. Cryoablation and immunotherapy of cancer[J].Curr Opin Biotechnol,2020,65: 60-64.
[53] Liu Q, Chen X, Qi M, et al. Combined cryoablation and PD-1 inhibitor synergistically enhance antitumor immune res ponses in Lewis lung adenocarcinoma mice via the PI3K/AKT/ mTOR pathway[J].Biochim Biophys Acta Mol Basis Dis,2024,1870 (7):167262.
[54] Yang X, Gao X, Xu C, et al. Cryoablation synergizes with anti-PD-1 immunotherapy induces an effective abscopal effe ct in murine model of cervical cancer[J].Transl Oncol, 2024, 51:102175.
[55] Li X, Xu J,Gu X,et al.Case Report:Antiangiogenic Thera py Plus Immune Checkpoint Inhibitors Combined With Intratum oral Cryoablation for Hepatocellular Carcinoma[J].Front Immu nol,2021,12:740790.
[56] Sardela de Miranda F,Castro M,Remmert N,Singh SP, Lay eequr Rahman R, Melkus MW. Leveraging cryoablation and check point inhibitors for high-risk triple negative breast cancer [J].Front Immunol,2023,14:1258873.
[57] Mustafa AR,Miyasato D,Wehrenberg-Klee E.Synergizing Thermal Ablation Modalities with Immunotherapy: Enough to Induce Systemic Antitumoral Immunity?[J].J Vasc Interv Radiol, 2024,35(2):185-197.
[58] Yu Z,Wang D,Qi Y,et al.Autologous-cancer-cryoablati on-mediated nanovaccine augments systematic immunotherapy [J].Mater Horiz,2023,10(5):1661-1677.
[59] Gu C, Wang X, Wang K, et al. Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer[J].J Immunother Canc er,2024,12(1).
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