实体肿瘤消融的免疫效应及联合免疫治疗的临床研究现状
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摘要
随着医学的不断进步,消融作为一种实体肿瘤微创治疗技术,而大量应用于临床并获得较好疗效.肿瘤消融亦可对肿瘤微环境产生影响,从而为肿瘤特异性免疫识别提供一个良好的环境,而联合免疫治疗可进一步增强其抗肿瘤免疫效应,改善长期疗效.关于肿瘤消融对机体免疫功能的影响以及免疫联合治疗近年来成为研究的热点,在临床病例中的应用逐渐增加,本文重点针对实体肿瘤消融的免疫效应及联合免疫治疗的临床研究文献进行总结,分析其临床应用现状.
Ablation, as a minimally invasive therapy for solid tumors, has been widely used in clinical practice and achieved satisfactory outcome. Tumor ablation has an effect on the tumor microenvironment so that a good environment for tumor specific immune recognition can be provided. Thus, combined immunotherapy can enhance the antitumor immune effect and improve the long-term outcome. The effect of tumor ablation on the immune function of the body and the combination of immunotherapy have become a hot topic in recent years. In this article, we will summarize the related clinical studies and comments on the effect of ablation of solid tumors on immune function and the status of combined immunotherapy.
Ablation, as a minimally invasive therapy for solid tumors, has been widely used in clinical practice and achieved satisfactory outcome. Tumor ablation has an effect on the tumor microenvironment so that a good environment for tumor specific immune recognition can be provided. Thus, combined immunotherapy can enhance the antitumor immune effect and improve the long-term outcome. The effect of tumor ablation on the immune function of the body and the combination of immunotherapy have become a hot topic in recent years. In this article, we will summarize the related clinical studies and comments on the effect of ablation of solid tumors on immune function and the status of combined immunotherapy.
引文
1孙立群,邓凤莲,邹建中.肿瘤消融治疗及其影像引导.中国医学影像学杂志2008;16:373-375[DOI:10.3969/J.ISSN.1005-5185.2008.05.018]
2 Turley SJ,Cremasco V,Astarita JL.Immunological hallmarks of stromal cells in the tumour microenvironment.Nat Rev Immunol 2015;15:669-682[PMID:26471778 DOI:10.1038/nri3902]
3尹健,朱光辉,单远洲,张明.动物模型在肿瘤微环境研究中的应用.肿瘤研究与临床2015;27:854-857[DOI:10.3760/cma.j.issn.1006-9801.2015.12.021]
4 Dong B,Liang P,Yu X,Su L,Yu D,Cheng Z,Zhang J.Percutaneous sonographically guided microwave coagulation therapy for hepatocellular carcinoma:results in 234 patients.AJR Am J Roentgenol 2003;180:1547-1555[PMID:12760916DOI:10.2212/ajr.180.6.1801547]
5 Haen S P,Pereira P L,Salih H R,Rammensee H G,Gouttefangeas C.More than just tumor destruction:immunomodulation by thermal ablation of cancer.Clin Dev Immunol 2011;2011:160250[PMID:22242035 DOI:10.1155/2011/160250]
6郭光辉,朱广义.抗肿瘤免疫与肝癌热消融相关性的研究进展.临床超声医学杂志2009;11:398-400[DOI:10.3969/j.issn.1008-6978.2009.06.013]
7 Zerbini A,Pilli M,Penna A,Pelosi G,Schianchi C,Molinari A,Schivazappa S,Zibera C,Fagnoni FF,Ferrari C,Missale G.Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses.Cancer Res 2006;66:1139-1146[PMID:16424051DOI:1158/0008-5472.CAN-05-2244]
8陈爱林,钟清华.微波消融治疗对肝癌患者免疫功能的影响.中国老年学杂志2012;32:3025-3026[DOI:10.3969/j.issn.1005-9209.2012.14.055]
9 Wu F,Wang ZB,Lu P,Xu ZL,Chen WZ,Zhu H,Jin CB.Activated anti-tumor immunity in cancer patients after high intensity focused ultrasound ablation.Ultrasound Med Biol2004;30:1217-1222[PMID:15550325 DOI:10.1016/j,ultrasme dbio.2004.08.003]
10 Fietta A M,Morosini M,Passadore I,Cascina A,Draghi P,Dore R,Rossi S,Pozzi E,Meloni F.Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer.Hum Immunol 2009;70:477-486[PMID:19332094 DOI:10.1016/j.humimm.2009.03.012]
11韩宗宏,曹建民,史东宏.肿瘤冷冻消融免疫效应研究的进展.介入放射学杂志2013;22:1055-1058[DOI:10.3969/j/issn.1008-794X.2013.12.024]
12何晓锋,肖越勇.肿瘤冷冻免疫及联合细胞免疫治疗的现状与进展.中华放射学杂志2013;47:381-384[DOI:10.3760/cma.j.issn.1005-1201.2013.04.025]
13 Si T,Guo Z,Hao X.Immunologic response to primary cryoablation of high-risk prostate cancer.Cryobiology 2008;57:66-71[PMID:18593573 DOI:10.1016/j.cryobiol.2008.06.003]
14宋光,王健,姚绍鑫.非小细胞肺癌患者CT引导下氩氦刀冷冻消融治疗前后外周血细胞因子和免疫功能的变化及意义.中国实验诊断学2016;20:564-566
15 Yamashita T,Hayakawa K,Hosokawa M,Kodama T,Inoue N,Tomita K,Kobayashi H.Enhanced tumor metastases in rats following cryosurgery of primary tumor.Gan 1982;73:222-228[PMID:7117753]
16 Sabel MS,Su G,Griffith KA,Chang AE.Rate of freeze alters the immunologic response after cryoablation of breast cancer.Ann Surg Oncol 2010;17:1187-1193[PMID:20033323 DOI:10.1254/S10434-009-0846-1]
17 LiG,Staveley-O’Carroll K F,Kimchi E T.Potential of Radio frequency Ablationin Combination with Immunotherapy in the Treatment of Hepatocellular Carcinoma.J Clin Trials 2016;6:257[PMID:28042519 DOI:10.4172/2167-0870.1000257]
18 Chen L,Sun J,Yang X.Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma:Current status.Cancer Lett 2016;370:78-84[PMID:26472630 DOI:10.1016/J.canlet.2015.09.020]
19 Gameiro SR,Higgins JP,Dreher MR,Woods DL,Reddy G,Wood BJ,Guha C,Hodge JW.Combination therapy with local radiofrequency ablation and systemic vaccine enhances antitumor immunity and mediates local and distal tumor regression.PLo S One 2013;8:e70417[PMID:23894654 DOI:10.1371/journal.pone.0070417]
20 Fagnoni FF,Zerbini A,Pelosi G,Missale G.Combination of radiofrequency ablation and immunotherapy.Front Biosci2008;13:369-381[PMID:17981554]
21 Cui J,Wang N,Zhao H,Jin H,Wang G,Niu C,Terunuma H,He H,Li W.Combination of radiofrequency ablation and sequential cellular immunotherapy improves progressionfree survival for patients with hepatocellular carcinoma.Int J Cancer 2014;134:342-351[PMID:23825037 DOI:10.1002/ijc.28372]
22 Nobuoka D,Motomura Y,Shirakawa H,Yoshikawa T,Kuronuma T,Takahashi M,Nakachi K,Ishii H,Furuse J,Gotohda N,Takahashi S,Nakagohri T,Konishi M,Kinoshita T,Komori H,Baba H,Fujiwara T,Nakatsura T.Radiofrequency ablation for hepatocellular carcinoma induces glypican-3peptide-specific cytotoxic T lymphocytes.Int J Oncol 2012;40:63-70[PMID:21922136 DOI:10.3892/ijo.2011.1202]
23 Lee JH,Lee JH,Lim YS,Yeon JE,Song TJ,Yu SJ,Gwak GY,Kim KM,Kim YJ,Lee JW,Yoon JH.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma.Gastroenterology 2015;148:1383-1391.e6[PMID:25747273 DOI:10.1053/j.gastro.2015.02.055]
24 Ma H,Zhang Y,Wang Q,Li Y,He J,Wang H,Sun J,Pan K,Chen M,Xia J.Therapeutic safety and effects of adjuvant autologous Retro Nectin activated killer cell immunotherapy for patients with primary hepatocellular carcinoma after radiofrequency ablation.Cancer Biol Ther 2010;9:903-907[PMID:20364106]
25 Yu MA,Liang P,Yu XL,Han ZY,Dong XJ,Wang YU,Cheng C,Li X.Multiple courses of immunotherapy with different immune cell types for patients with hepatocellular carcinoma after microwave ablation.Exp Ther Med 2015;10:1460-1466[PMID:26622507 DOI:10.3892/etm.2015.2681]
26周佩,梁萍,董宝玮,于晓玲,于杰,徐迎新.微波消融联合过继免疫治疗肝癌的临床.同济大学学报2012;33:71-77[DOI:10.3969/j.issn.1008-0392.2012.04.016]
27 Zhou P,Liang P,Dong B,Yu X,Han Z,Xu Y.PhaseⅠclinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma.Cancer Biol Ther 2011;11:450-456[PMID:21258206]
28 Lin M,Xu K,Liang S,Wang X,Liang Y,Zhang M,Chen J,Niu L.Prospective study of percutaneous cryoablation combined with allogenic NK cell immunotherapy for advanced renal cell cancer.Immunol Lett 2017;184:98-104[PMID:28274792DOI:10.1016/j.imlet.2017.03.004]
29 Liang S,Niu L,Xu K,Wang X,Liang Y,Zhang M,Chen J,Lin M.Tumorcryo ablationin combination with natural killer cells therapy and Herceptin in patients with HER2-overexpressing recurrent breast cancer.Mol Immunol 2017;92:45-53[PMID:29040918 DOI:10.1016/j.molimm.2017.10.003]
2 Turley SJ,Cremasco V,Astarita JL.Immunological hallmarks of stromal cells in the tumour microenvironment.Nat Rev Immunol 2015;15:669-682[PMID:26471778 DOI:10.1038/nri3902]
3尹健,朱光辉,单远洲,张明.动物模型在肿瘤微环境研究中的应用.肿瘤研究与临床2015;27:854-857[DOI:10.3760/cma.j.issn.1006-9801.2015.12.021]
4 Dong B,Liang P,Yu X,Su L,Yu D,Cheng Z,Zhang J.Percutaneous sonographically guided microwave coagulation therapy for hepatocellular carcinoma:results in 234 patients.AJR Am J Roentgenol 2003;180:1547-1555[PMID:12760916DOI:10.2212/ajr.180.6.1801547]
5 Haen S P,Pereira P L,Salih H R,Rammensee H G,Gouttefangeas C.More than just tumor destruction:immunomodulation by thermal ablation of cancer.Clin Dev Immunol 2011;2011:160250[PMID:22242035 DOI:10.1155/2011/160250]
6郭光辉,朱广义.抗肿瘤免疫与肝癌热消融相关性的研究进展.临床超声医学杂志2009;11:398-400[DOI:10.3969/j.issn.1008-6978.2009.06.013]
7 Zerbini A,Pilli M,Penna A,Pelosi G,Schianchi C,Molinari A,Schivazappa S,Zibera C,Fagnoni FF,Ferrari C,Missale G.Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses.Cancer Res 2006;66:1139-1146[PMID:16424051DOI:1158/0008-5472.CAN-05-2244]
8陈爱林,钟清华.微波消融治疗对肝癌患者免疫功能的影响.中国老年学杂志2012;32:3025-3026[DOI:10.3969/j.issn.1005-9209.2012.14.055]
9 Wu F,Wang ZB,Lu P,Xu ZL,Chen WZ,Zhu H,Jin CB.Activated anti-tumor immunity in cancer patients after high intensity focused ultrasound ablation.Ultrasound Med Biol2004;30:1217-1222[PMID:15550325 DOI:10.1016/j,ultrasme dbio.2004.08.003]
10 Fietta A M,Morosini M,Passadore I,Cascina A,Draghi P,Dore R,Rossi S,Pozzi E,Meloni F.Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer.Hum Immunol 2009;70:477-486[PMID:19332094 DOI:10.1016/j.humimm.2009.03.012]
11韩宗宏,曹建民,史东宏.肿瘤冷冻消融免疫效应研究的进展.介入放射学杂志2013;22:1055-1058[DOI:10.3969/j/issn.1008-794X.2013.12.024]
12何晓锋,肖越勇.肿瘤冷冻免疫及联合细胞免疫治疗的现状与进展.中华放射学杂志2013;47:381-384[DOI:10.3760/cma.j.issn.1005-1201.2013.04.025]
13 Si T,Guo Z,Hao X.Immunologic response to primary cryoablation of high-risk prostate cancer.Cryobiology 2008;57:66-71[PMID:18593573 DOI:10.1016/j.cryobiol.2008.06.003]
14宋光,王健,姚绍鑫.非小细胞肺癌患者CT引导下氩氦刀冷冻消融治疗前后外周血细胞因子和免疫功能的变化及意义.中国实验诊断学2016;20:564-566
15 Yamashita T,Hayakawa K,Hosokawa M,Kodama T,Inoue N,Tomita K,Kobayashi H.Enhanced tumor metastases in rats following cryosurgery of primary tumor.Gan 1982;73:222-228[PMID:7117753]
16 Sabel MS,Su G,Griffith KA,Chang AE.Rate of freeze alters the immunologic response after cryoablation of breast cancer.Ann Surg Oncol 2010;17:1187-1193[PMID:20033323 DOI:10.1254/S10434-009-0846-1]
17 LiG,Staveley-O’Carroll K F,Kimchi E T.Potential of Radio frequency Ablationin Combination with Immunotherapy in the Treatment of Hepatocellular Carcinoma.J Clin Trials 2016;6:257[PMID:28042519 DOI:10.4172/2167-0870.1000257]
18 Chen L,Sun J,Yang X.Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma:Current status.Cancer Lett 2016;370:78-84[PMID:26472630 DOI:10.1016/J.canlet.2015.09.020]
19 Gameiro SR,Higgins JP,Dreher MR,Woods DL,Reddy G,Wood BJ,Guha C,Hodge JW.Combination therapy with local radiofrequency ablation and systemic vaccine enhances antitumor immunity and mediates local and distal tumor regression.PLo S One 2013;8:e70417[PMID:23894654 DOI:10.1371/journal.pone.0070417]
20 Fagnoni FF,Zerbini A,Pelosi G,Missale G.Combination of radiofrequency ablation and immunotherapy.Front Biosci2008;13:369-381[PMID:17981554]
21 Cui J,Wang N,Zhao H,Jin H,Wang G,Niu C,Terunuma H,He H,Li W.Combination of radiofrequency ablation and sequential cellular immunotherapy improves progressionfree survival for patients with hepatocellular carcinoma.Int J Cancer 2014;134:342-351[PMID:23825037 DOI:10.1002/ijc.28372]
22 Nobuoka D,Motomura Y,Shirakawa H,Yoshikawa T,Kuronuma T,Takahashi M,Nakachi K,Ishii H,Furuse J,Gotohda N,Takahashi S,Nakagohri T,Konishi M,Kinoshita T,Komori H,Baba H,Fujiwara T,Nakatsura T.Radiofrequency ablation for hepatocellular carcinoma induces glypican-3peptide-specific cytotoxic T lymphocytes.Int J Oncol 2012;40:63-70[PMID:21922136 DOI:10.3892/ijo.2011.1202]
23 Lee JH,Lee JH,Lim YS,Yeon JE,Song TJ,Yu SJ,Gwak GY,Kim KM,Kim YJ,Lee JW,Yoon JH.Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma.Gastroenterology 2015;148:1383-1391.e6[PMID:25747273 DOI:10.1053/j.gastro.2015.02.055]
24 Ma H,Zhang Y,Wang Q,Li Y,He J,Wang H,Sun J,Pan K,Chen M,Xia J.Therapeutic safety and effects of adjuvant autologous Retro Nectin activated killer cell immunotherapy for patients with primary hepatocellular carcinoma after radiofrequency ablation.Cancer Biol Ther 2010;9:903-907[PMID:20364106]
25 Yu MA,Liang P,Yu XL,Han ZY,Dong XJ,Wang YU,Cheng C,Li X.Multiple courses of immunotherapy with different immune cell types for patients with hepatocellular carcinoma after microwave ablation.Exp Ther Med 2015;10:1460-1466[PMID:26622507 DOI:10.3892/etm.2015.2681]
26周佩,梁萍,董宝玮,于晓玲,于杰,徐迎新.微波消融联合过继免疫治疗肝癌的临床.同济大学学报2012;33:71-77[DOI:10.3969/j.issn.1008-0392.2012.04.016]
27 Zhou P,Liang P,Dong B,Yu X,Han Z,Xu Y.PhaseⅠclinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma.Cancer Biol Ther 2011;11:450-456[PMID:21258206]
28 Lin M,Xu K,Liang S,Wang X,Liang Y,Zhang M,Chen J,Niu L.Prospective study of percutaneous cryoablation combined with allogenic NK cell immunotherapy for advanced renal cell cancer.Immunol Lett 2017;184:98-104[PMID:28274792DOI:10.1016/j.imlet.2017.03.004]
29 Liang S,Niu L,Xu K,Wang X,Liang Y,Zhang M,Chen J,Lin M.Tumorcryo ablationin combination with natural killer cells therapy and Herceptin in patients with HER2-overexpressing recurrent breast cancer.Mol Immunol 2017;92:45-53[PMID:29040918 DOI:10.1016/j.molimm.2017.10.003]