摘要
目前主要的免疫治疗包括溶瘤病毒、免疫检查点抑制剂、细胞因子、肿瘤疫苗、过继性免疫细胞等。溶瘤病毒是一种很有前景的抗肿瘤新兴制剂,通过选择性杀伤肿瘤细胞、诱导机体产生特异的抗肿瘤免疫反应来实现治疗肿瘤的目的。Talimogene laherparepvec (T-VEC)是第一个被批准用于治疗转移性恶性黑色素瘤的溶瘤病毒。免疫检查点抑制剂以其显著的临床疗效而备受瞩目。免疫检查点抑制剂在许多实体瘤中取得了很好的疗效,包括CTLA-4及其抑制剂、PD-1及其抑制剂等。T-VEC与免疫检查点抑制剂抗癌优势互补。溶瘤病毒与联合免疫检查点抑制剂在恶性黑色素瘤的应用包括T-VEC与ipilimumab联合治疗、T-VEC与pembrolizumab联合治疗等。通过将溶瘤病毒与免疫检查点抑制剂联合能够显著延长肿瘤患者生存期。本文对两种免疫疗法联合治疗的合理性及两者联合在恶性黑色素瘤中的应用进展作一综述。
引文
[1]DUNN GP,BRUCE AT,IKEDA H,et al.Cancer immunoediting:from immunosurveillance to tumor escape[J].Nat Immunol,2002,3(11):991-998.DOI:10.1038/ni1102-991.
[2]WALDHAUER I,STEINLE A.NK cells and cancer immunosurveillance[J].Oncogene,2008,27(45):5932-5943.DOI:10.1038/onc.2008.267.
[3]ZOU C,ZHAO P,XIAO Z,et al.γδT cells in cancer immunotherapy[J].Oncotarget,2017,8(5):8900-8909.DOI:10.18632/oncotarget.13051.
[4]RAPHAEL I,NALAWADE S,EAGAR T N,et al.T cell subsets and their signature cytokines in autoimmune and inflammatory diseases[J].Cytokine,2015,74(1):5-17.DOI:10.1016/j.cyto.2014.09.011.
[5]FRIDMAN WH,PAGèS F,SAUTèS-FRIDMAN C,et al.The immune contexture in human tumours:impact on clinical outcome[J].Nat Rev Cancer,2012,12(4):298-306.DOI:10.1038/nrc3245.
[6]VAN DER BURG SH,ARENS R,OSSENDORP F,et al.Vaccines for established cancer:overcoming the challenges posed by immune evasion[J].Nat RevCancer,2016,16(4):219-233.DOI:10.1038/nrc.2016.16.
[7]PITT J M,MARABELLE A,EGGERMONT A,et al.Targeting the tumor microenvironment:removing obstruction to anticancer immune responses and immunotherapy[J].Ann Oncol,2016,27(8):1482-1492.DOI:10.1093/annonc/mdw168.
[8]THORNE S H,HERMISTON T,KIRN D.Oncolytic virotherapy:approaches to tumor targeting and enhancing antitumor effects[J].Semin Oncol,2005,32(6):537-548.DOI:10.1053/j.seminoncol.2005.09.007.
[9]PRESTWICH R J,ERRINGTON F,DIAZ R M,et al.The case of oncolytic viruses versus the immune system:waiting on the judgment of Solomon[J].Hum Gene Ther,2009,20(10):1119-1132.DOI:10.1089/hum.2009.135.
[10]魏智民,陈寅,焦顺昌.免疫检查点抑制剂在肺癌治疗中的应用研究进展[J].中华老年多器官疾病杂志,2018,17(5):383-388.DOI:10.11915/j.issn.1671-5403.2018.05.086.
[11]孙礼媛,刘荻萩,王晓钧,等.溶瘤病毒的治疗进展[J].医学综述,2017,23(2):235-239.DOI:10.3969/j.issn.1006-2084.2017.02.007.
[12]MATTILA R K,HARILA K,KANGAS S M,et al.An investigation of herpes simplex virus type 1 latency in a novel mouse dorsal root ganglion model suggests a role for ICP34.5 in reactivation[J].J Gen Virol,2015,96(8):2304-2313.DOI:10.1099/vir.0.000138.
[13]CODY J J,SCATURRO P,CANTOR A B,et al.Preclinical evaluation of oncolyticδγ(1)34.5 herpes simplex virus expressing interleukin-12 for therapy of breast cancer brain metastases[J].Int JBreast Cancer,2012,2012:1-12.DOI:10.1155/2012/628697.
[14]RAAFAT N,SADOWSKI-CRON C,MENGUS C,et al.Preventing vaccinia virus class-I epitopes presentation by HSV-ICP47 enhances the immunogenicity of a TAP-independent cancer vaccine epitope[J].Int J Cancer,2012,131(5):E659-669.DOI:10.1002/ijc.27362.
[15]BHATTACHARYA P,THIRUPPATHI M,ELSHABRAWY H A,et al.GM-CSF:an immune modulatory cytokine that can suppress autoimmunity[J].Cytokine,2015,75(2):261-271.DOI:10.1016/j.cyto.2015.05.030.
[16]ANDTBACKA R H,KAUFMAN H L,COLLICHIO F,et al.Talimogene laherparepvec improves durable response rate in patients with advanced melanoma[J].J Clin Oncol,2015,33(25):2780-2788.DOI:10.1200/JCO.2014.58.3377.
[17]GREIG S L.Talimogene laherparepvec:first global approval[J].Drugs,2016,76(1):147-154.DOI:10.1007/s40265-015-0522-7.
[18]郭静,曲鑫建,伍会健.肿瘤免疫疗法中免疫检查点的研究进展[J].生理科学进展,2017,48(4):287-293.DOI:10.3969/j.issn.0559-7765.2017.04.011.
[19]许标波,贺毅憬,王韦力.肿瘤免疫检查点抑制剂临床治疗的研究进展[J].中国临床药理学与治疗学,2016,21(2):218-224.
[20]VESELY M D,KERSHAW M H,SCHREIBER R D,et al.Natural innate and adaptive immunity to cancer[J].Annu Rev Immunol,2011,29:235-271.DOI:10.1146/annurev-immunol-031210-101324.
[21]QURESHI O S,ZHENG Y,NAKAMURA K,et al.Trans-endocytosis of CD80 and CD86:a molecular basis for the cell-extrinsic function of CTLA-4[J].Science,2011,332(6029):600-603.DOI:10.1126/science.1202947.
[22]HODI FS,O’DAY S J,MCDERMOTT D F,et al.Improved survival with ipilimumab in patients with metastatic melanoma[J].N Engl J Med,2010,363(8):711-723.DOI:10.1056/NEJMoa1003466.
[23]ROBERT C,THOMAS L,BONDARENKO I,et al.Ipilimumab plus dacarbazine for previously untreated metastatic melanoma[J].N Engl J Med,2011,364(26):2517-2526.DOI:10.1056/NEJ-Moa1104621.
[24]SHI L,CHEN S,YANG L,et al.The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies[J].J Hematol Oncol,2013,6(1):74.DOI:10.1186/1756-8722-6-74.
[25]FRANKLIN C,LIVINGSTONE E,ROESCH A.Immunotherapy in melanoma:recent advances and future directions[J].Eur J Surg Oncol,2017,43(3):604-611.DOI:10.1016/j.ejso.2016.07.145.
[26]ROBERT C,LONG GV,BRADY B,et al.Nivolumab in previously untreated melanoma without BRAF mutation[J].N Engl J Med,2015,372(4):320-330.DOI:10.1056/NEJMoa1412082.
[27]WEBER JS,D’ANGELO S P,MINOR D,et al.Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment(CheckMate 037):a randomised,controlled,open-label,phase 3 trial[J].Lancet Oncol,2015,16(4):375-384.DOI:10.1016/S1470-2045(15)70076-8.
[28]张力.非小细胞肺癌免疫治疗-风景靓丽,更需追求完美[J].华西医学,2018,33(4):375-378.
[29]郭子寒,杜琼,戴贤春等.免疫检查点抑制剂的发展概况[J].上海医药,2018,39(5):10-13.
[30]李广欣,王婧,曹邦伟.免疫检查点抑制剂治疗肝细胞癌的研究现状与进展[J].中国医院用药评价与分析,2018,18(4):440-45.DOI:10.14009/j.issn.1672-2124.2018.04.004.
[31]SAMSON A,SCOTT KJ,TAGGART D,et al.Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade[J].Sci Transl Med,2018,10(422).pii:eaam7577.DOI:10.1126/scitranslmed.aam7577.
[32]PRESTWICH R J,ERRINGTON F,ILETT E J,et al.Tumor infection by oncolytic reovirus primes adaptive antitumor immunity[J].Clin Cancer Res,2008,14(22):7358-66.DOI:10.1158/1078-0432.CCR-08-0831.
[33]RIBAS A,DUMMER R,PUZANOV I,et al.Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy[J].Cell,2017,170(6):1109-1119.DOI:10.1016/j.cell.2017.08.027.
[34]魏智民,陈寅,焦顺昌.免疫检查点抑制剂在肺癌治疗中的应用研究进展[J].中华老年多器官疾病杂志,2018,17(5):383-388.DOI:10.11915/j.issn.1671-5403.2018.05.086.
[35]ZAMARIN D,RICCA J M,SADEKOVA S.PD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy[J].JClin Invest,2018,128(4):1413-1428.DOI:10.1172/JCI98047.Epub2018 Mar 5.
[36]PUZANOV I,MILHEM M,MINOR D,et al.Talimogene laherparepvec in combination with ipilimumab in previously untreated,unresectable stage IIIB-IV melanoma[J].J Clin Oncol,2016,34(22):2619-2626.DOI:10.1200/JCO.2016.67.1529.
