冷冻消融结合免疫治疗:实现抗肿瘤效应最大化
黄若彤, 刘宝林#*
(上海理工大学生物系统热科学研究所,上海 200093)
Cryoablation Combined with Immunotherapy: Maximizing Anti-Tumor Effects
Huang Ruotong, Lui Baolin#*
(Institute of Biothermal and Technology,University of Shanghai for Science and Technology, Shanghai 200093, China)
摘要 近年来,基于能量治疗的肿瘤消融技术应用愈加广泛。其中,冷冻消融技术是通过对探针的快速冷却,有效破坏肿瘤组织。然而,留在原位的肿瘤碎片还会释放出大量抗原,激活免疫细胞,诱导产生抗肿瘤免疫反应。但因冷冻消融参数条件设置的不同,会影响所触发的免疫反应,且因诱发产生的免疫反应的强度和可持续性不足,难以有效抑制肿瘤的复发和转移瘤的生长。综述冷冻消融治疗肿瘤的机制,包括直接细胞损伤、血管损伤和免疫调节,其中免疫调节对肿瘤治疗的良好预后产生重要影响;阐述影响免疫调节效果的冷冻消融因素,探寻冷冻消融治疗后产生免疫反应的最佳条件;概述冷冻消融联合免疫治疗的研究进展,并且探讨联合抗肿瘤治疗的新策略。
关键词 :
冷冻消融 ,
免疫机制 ,
免疫治疗 ,
联合治疗
Abstract :In recent years, energy therapy-based tumor ablation techniques have become more widely used. Among them, the cryoablation technique can effectively destroy tumors by rapid cooling of the probe, and the tumor mass left in situ would release a lot of antigens to activate immune cells, inducing the generation of anti-tumor immune responses. However, the immune response triggered by cryoablation is subjected to its conditional setting, and the intensity and sustainability of the immune response are insufficient to suppress tumor recurrence and the growth of metastases. Hence, this review focuses on the mechanisms of cryoablation for tumors, including direct cell injury, vascular injury, and immunomodulation, in which immunomodulation has a significant impact on the favorable prognosis of tumor therapy. Cryoablation factors affecting immune efficacy were further introduced to discuss the optimal conditions for generating immune response after treatment. The research progress of cryoablation combined with immunotherapy is summarized to propose new strategies for tumor treatment.
Key words :
cryoablation
immune mechanism
immunotherapy
combination therapy
收稿日期: 2022-06-14
基金资助: 上海市肿瘤能量治疗技术与器械协同创新中心
通讯作者:
* E-mail:blliuk@usst.edu.cn
作者简介 : # 中国生物医学工程学会会员
[1] Soerjomataram I, Bray F. Planning for tomorrow: global cancer incidence and the role of prevention 2020-2070[J]. Nature Reviews Clinical Oncology, 2021, 18(10): 663-672. [2] Xia Changfa, Dong Xuesi, Li He, et al. Cancer statistics in china and united states, 2022: profiles, trends, and determinants[J]. Chinese Medical Journal, 2022, 135(5): 584-590. [3] Arnott, James. Practical illustrations of the remedial efficacy of a very low or an?Sthetic temperature.—i. In cancer[J]. Lancet, 1850, 56(1411): 316-318. [4] Gage AA. History of cryosurgery[C] //Seminars in Surgical Oncology. New York: John Wiley & Sons, Inc., 1998: 99-109. [5] Allington H. Liquid nitrogen in the treatment of skin diseases[J]. California Medicine, 1950, 72(3): 153. [6] Cooper IS. A new method of destruction or extirpation of benign or malignant tissues[J]. N Engl J Med, 1963, 268: 743-749. [7] Weber SM, Lee FT. Cryoablation: history, mechanism of action, and guidance modalities[M]//Tumor Ablation. New York: Springer, 2005: 250-265. [8] Torre D. Alternate cryogens for cryosurgery[J]. The Journal of Dermatologic Surgery, 1975, 1(2): 56-58. [9] 李鸿鹏, 李铁军. 冷冻治疗的研究[J]. 医学综述, 2019, 25(2): 317-321. [10] Baust J, Gage A, Johansen TB, et al. Mechanisms of cryoablation: clinical consequences on malignant tumors[J]. Cryobiology, 2014, 68(1): 1-11. [11] Hoffmann NE, Bischof JC. The cryobiology of cryosurgical injury[J]. Urology, 2002, 60(2): 40-49. [12] Shao Qi, O'flanagan S, Lam T, et al. Engineering T cell response to cancer antigens by choice of focal therapeutic conditions[J]. International Journal of Hyperthermia, 2019, 36(1): 130-138. [13] Chapman WC, Debelak JP, Pinson CW, et al. Hepatic cryoablation, but not radiofrequency ablation, results in lung inflammation[J]. Annals of Surgery, 2000, 231(5): 752-761. [14] Yantorno C, Soanes W, Gonder M, et al. Studies in cryo-immunology: I. The production of antibodies to urogenital tissue in consequence of freezing treatment[J]. Immunology, 1967, 12(4): 395-410. [15] Yang Xueling, Guo Yongfei, Guo Zhi, et al. Cryoablation inhibition of distant untreated tumors (abscopal effect) is immune mediated[J]. Oncotarget, 2019, 10(41): 4180-4190. [16] Urano M, Tanaka C, Sugiyama Y, et al. Antitumor effects of residual tumor after cryoablation: the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model[J]. Cryobiology, 2003, 46(3): 238-245. [17] Yakkala C, Chiang CLL, Kandalaft L, et al. Cryoablation and immunotherapy: an enthralling synergy to confront the tumors[J]. Frontiers in Immunology, 2019,10: 2283. [18] Mazur P, Leibo S, Chu E. A two-factor hypothesis of freezing injury: evidence from chinese hamster tissue-culture cells[J]. Experimental Cell Research, 1972, 71(2): 345-355. [19] Gage AA, Baust J. Mechanisms of tissue injury in cryosurgery[J]. Cryobiology, 1998, 37(3): 171-186. [20] Meryman HT. Modified model for the mechanism of freezing injury in erythrocytes[J]. Nature, 1968, 218(5139): 333-336. [21] Mahnken AH, König AM, Figiel JH. Current Technique and Application of Percutaneous Cryotherapy[C] // Stuttgart. RöFo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der Bildgebenden Verfahren. New York:© Georg Thieme Verlag KG, 2018: 836-846. [22] Weber SM, Lee Jr FT, Chinn DO, et al. Perivascular and intralesional tissue necrosis after hepatic cryoablation: results in a porcine model[J]. Surgery, 1997, 122(4): 742-747. [23] Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy[J]. Nature Reviews Cancer, 2014, 14(3): 199-208. [24] Viorritto IC, Nikolov NP, Siegel RM. Autoimmunity versus tolerance: can dying cells tip the balance?[J]. Clinical Immunology, 2007, 122(2): 125-134. [25] Soanes WA, Gonder MJ, Ablin R. A possible immuno-cryothermic response in prostatic cancer[J]. Clinical Radiology, 1970, 21(3): 253-255. [26] Sabel MS. Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses[J]. Cryobiology, 2009, 58(1): 1-11. [27] Gardner A, Ruffell B. Dendritic cells and cancer immunity[J]. Trends in Immunology, 2016, 37(12): 855-865. [28] Bevan MJ. Cross-priming for a secondary cytotoxic response to minor h antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay[J]. The Journal of Experimental Medicine, 1976, 143(5): 1283-1288. [29] Flutter B, Fu HM, Wedderburn L, et al. An extra molecule in addition to human tapsin is required for surface expression of β2m linked HLA-B4402 on murine cell[J]. Molecular Immunology, 2007, 44(14): 3528-3536. [30] Merad M, Sathe P, Helft J, et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting[J]. Annual Review of Immunology, 2013, 31: 563-604. [31] Maccini M, Sehrt D, Pompeo A, et al. Biophysiologic considerations in cryoablation: a practical mechanistic molecular review[J]. International Braz J Urol, 2011, 37: 693-696. [32] Clarke DM, Robilotto AT, Rhee E, et al. Cryoablation of renal cancer: variables involved in freezing-induced cell death[J]. Technology in Cancer Research & Treatment, 2007, 6(2): 69-79. [33] Savill J, Dransfield I, Gregory C, et al. A blast from the past: clearance of apoptotic cells regulates immune responses[J]. Nature Reviews Immunology, 2002, 2(12): 965-975. [34] Sauter B, Albert ML, Francisco L, et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells[J]. The Journal of Experimental Medicine, 2000, 191(3): 423-434. [35] Scheffer SR, Nave H, Korangy F, et al. Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo[J]. International Journal of Cancer, 2003, 103(2): 205-211. [36] Spörri R, Reis E Sousa C. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function[J]. Nature Immunology, 2005, 6(2): 163-170. [37] Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer[J]. Annual Review of Immunology, 2011, 29: 235-271. [38] Sabel MS, Su G, Griffith KA, et al. Rate of freeze alters the immunologic response after cryoablation of breast cancer[J]. Annals of Surgical Oncology, 2010, 17(4): 1187-1193. [39] Yakkala C, Dagher J, Sempoux C, et al. Rate of freeze impacts the survival and immune responses post cryoablation of melanoma[J]. Frontiers in Immunology, 2021, 12: 2038. [40] Yiu W-K, Basco MT, Aruny JE, et al. Cryosurgery: A review[J]. International Journal of Angiology, 2007, 16(1): 1-6. [41] Stewart G, Preketes A, Horton M, et al. Hepatic cryotherapy:double-freeze cycles achieve greater hepatocellular injury in man[J]. Cryobiology, 1995, 32(3): 215-219. [42] Mala T, Edwin B, Tillung T, et al. Percutaneous cryoablation of colorectal liver metastases: potentiated by two consecutive freeze-thaw cycles[J]. Cryobiology, 2003, 46(1): 99-102. [43] Takahashi Y, Izumi Y, Matsutani N, et al. Optimized magnitude of cryosurgery facilitating anti-tumor immunoreaction in a mouse model of lewis lung cancer[J]. Cancer Immunology, Immunotherapy, 2016, 65(8): 973-982. [44] Mala T. Cryoablation of liver tumours - a review of mechanisms, techniques and clinical outcome[J]. Minimally Invasive Therapy & Allied Technologies, 2006, 15(1): 9-17. [45] Robilotto A, Baust J, Van Buskirk R, et al. Temperature-dependent activation of differential apoptotic pathways during cryoablation in a human prostate cancer model[J]. Prostate Cancer and Prostatic Diseases, 2013, 16(1): 41-49. [46] Aarts B, Klompenhouwer E, Rice S, et al. Cryoablation and immunotherapy: an overview of evidence on its synergy[J]. Insights Into Imaging, 2019, 10(1): 1-12. [47] Van Den Bijgaart RJE, Schuurmans F, Fütterer JJ, et al. Immune modulation plus tumor ablation: adjuvants and antibodies to prime and boost anti-tumor immunity in situ[J]. Frontiers in Immunology, 2021, 12: 1156. [48] Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance[J]. Proceedings of the National Academy of Sciences, 2002, 99(1): 351-358. [49] Alteber Z, Azulay M, Cafri G, et al. Cryoimmunotherapy with local co-administration of ex vivo generated dendritic cells and CpG-ODN immune adjuvant, elicits a specific antitumor immunity[J]. Cancer Immunology, Immunotherapy, 2014, 63(4): 369-380. [50] Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy[J]. Cancer Cell, 2015, 27(4): 450-461. [51] Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nature Reviews Cancer, 2012, 12(4): 252-264. [52] Benzon B, Glavaris SA, Simons BW, et al. Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer[J]. Prostate Cancer Prostatic Diseases, 2018, 21(1): 126-136. [53] Mcarthur HL, Diab A, Page DB, et al. A pilot study of preoperative single-dose ipilimumab and/or cryoablation in women with early-stage breast cancer with comprehensive immune profiling[J]. Clinical Cancer Research, 2016, 22(23): 5729-5737. [54] Marin-Acevedo JA, Dholaria B, Soyano AE, et al. Next generation of immune checkpoint therapy in cancer: new developments and challenges[J]. Journal of Hematology & Oncology, 2018, 11(1): 1-20. [55] Cheng Min, Chen Yongyan, Xiao Weihua, et al. NK cell-based immunotherapy for malignant diseases[J]. Cellular & Molecular Immunology, 2013, 10(3): 230-252. [56] Lodoen MB, Lanier LL. Viral modulation of NK cell immunity[J]. Nature Reviews Microbiology, 2005, 3(1): 59-69. [57] Drake CG, Jaffee E, Pardoll DM. Mechanisms of immune evasion by tumors[J]. Advances In Immunology, 2006, 90: 51-81. [58] Davis CT, Rizzieri D. Immunotherapeutic applications of NK cells[J]. Pharmaceuticals, 2015, 8(2): 250-256. [59] Liang Shuzhen, Niu Lizhi, Xu Kecheng, et al. Tumor cryoablation in combination with natural killer cells therapy and herceptin in patients with HER2-overexpressing recurrent breast cancer[J]. Molecular Immunology, 2017, 92: 45-53. [60] Yin Zhilin, Lu Guohui, Xiao Zhenyong, et al. Antitumor efficacy of argon-helium cryoablation-generated dendritic cell vaccine in glioma[J]. Neuroreport, 2014, 25(4): 199-204. [61] Cebula H, Noel G, Garnon J, et al. The cryo-immunologic effect: a therapeutic advance in the treatment of glioblastomas?[J]. Neurochirurgie, 2020, 66(6): 455-460. [62] Constantino J, Gomes C, Falco A, et al. Antitumor dendritic cell-based vaccines: lessons from 20 years of clinical trials and future perspectives[J]. Translational Research, 2016, 168: 74-95. [63] Machlenkin A, Goldberger O, Tirosh B, et al. Combined dendritic cell cryotherapy of tumor induces systemic antimetastatic immunity[J]. Clinical Cancer Research, 2005, 11(13): 4955-4961. [64] Den Brok M, Sutmuller RPM, Nierkens S, et al. Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity[J]. British Journal of Cancer, 2006, 95(7): 896-905. [65] Introna M. CIK as therapeutic agents against tumors[J]. Journal of Autoimmunity, 2017, 85: 32-44. [66] Mesiano G, Todorovic M, Gammaitoni L, et al. Cytokine-induced killer (CIK) cells as feasible and effective adoptive immunotherapy for the treatment of solid tumors[J]. Expert Opinion on Biological Therapy, 2012, 12(6): 673-684. [67] Niu Lizhi, Chen Jibing, He Lihua, et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic pancreatic cancer[J]. Pancreas, 2013, 42(7): 1143-1149. [68] Yuan Yuanying, Niu Lizhi, Mu Feng, et al. Therapeutic outcomes of combining cryotherapy, chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer[J]. Cryobiology, 2013, 67(2): 235-240. [69] Perica K, Varela JC, Oelke M, et al. Adoptive T cell immunotherapy for cancer[J]. Rambam Maimonides Medical Journal, 2015, 6(1): 1-9. [70] Gooden MJ, De Bock GH, Leffers N, et al. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis[J]. British Journal of Cancer, 2011, 105(1): 93-103. [71] Met Ö, Jensen KM, Chamberlain CA, et al. Principles of adoptive T cell therapy in cancer[C] //Seminars in Immunopathology. Berlin Heidelberg: Springer, 2019: 49-58. [72] Sabel MS, Arora A, Su G, et al. Adoptive immunotherapy of breast cancer with lymph node cells primed by cryoablation of the primary tumor[J]. Cryobiology, 2006, 53(3): 360-366. [73] Armitage JO. Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor[J]. Blood, 1998, 92(12): 4491-4508. [74] Disis ML, Bernhard H, Shiota FM, et al. Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines[J]. Blood, 1996, 88(1): 202-210. [75] Xu Hongchao, Wang Qifu, Lin Chunnan, et al. Synergism between cryoablation and GM-CSF: enhanced immune function of splenic dendritic cells in mice with glioma[J]. Neuroreport, 2015, 26(6): 346-353. [76] Thakur A, Littrup P, Paul EN, et al. Induction of specific cellular and humoral responses against renal cell carcinoma after combination therapy with cryoablation and granulocyte-macrophage colony stimulating factor: a pilot study[J]. Journal of Immunotherapy, 2011, 34(5): 457-467. [77] Si Tongguo, Guo Zhi, Hao Xishan. Combined cryoablation and GM-CSF treatment for metastatic hormone refractory prostate cancer[J]. Journal of Immunotherapy, 2009, 32(1): 86-91. [78] Zhang Jieying, Shi Zhaopeng, Xu Xiang, et al. The influence of microenvironment on tumor immunotherapy[J]. The FEBS Journal, 2019, 286(21): 4160-4175. [79] Li Shang, Zhang Zhibi, Lai WingFu, et al. How to overcome the side effects of tumor immunotherapy[J]. Biomedicine & Pharmacotherapy, 2020, 130: 110639.
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