朱丽珍,房雪峰,袁瑛

• 1:浙江大学医学院附属第二医院肿瘤内科

摘要(Abstract)：

<正>近年来,肿瘤免疫治疗特别是免疫靶向药物在恶性肿瘤治疗方面显示出振奋人心的效果及巨大的潜能。自2010年肿瘤疫苗sipuleucel-T被美国FDA批准用于治疗前列腺癌后[1],肿瘤免疫治疗的新方法不断被研发出来,越来越多的免疫治疗方法在临

关键词(KeyWords)： 结直肠肿瘤/治疗;肿瘤转移;结直肠肿瘤/继发性;免疫疗法;治疗结果

Abstract:

Keywords:

基金项目(Foundation): 国家“十二五”支撑计划(2014BAI09B07);; 浙江省重点研发项目(2016C03017)

作者(Author): 朱丽珍,房雪峰,袁瑛

DOI: 10.13267/j.cnki.syzlzz.2017.02.004

参考文献(References)：

• [1]Kantoff PW,Higano CS,Shore ND,et al.Sipuleucel-T immunotherapy for castration-resistant prostate cancer[J].N Engl J Med,2010,363(5):411-422.
• [2]Hamid O,Robert C,Daud A,et al.Safety and tumor responses with lambrolizumab(anti-PD-1)in melanoma[J].N Engl J Med,2013,369(2):134-144.
• [3]Herbst RS,Soria JC,Kowanetz M,et al.Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J].Nature,2014,515(7528):563-567.
• [4]Tumeh PC,Harview CL,Yearley JH,et al.PD-1 blockade induces responses by inhibiting adaptive immune resistance[J].Nature,2014,515(7528):568-571.
• [5]Le DT,Uram JN,Wang H,et al.PD-1 blockade in tumors with mismatch-repair deficiency[J].N Engl J Med,2015,372(26):2509-2520.
• [6]H9rig H,Lee DS,Conkright W,et al.PhaseⅠclinical trial of a recombinant canarypoxvirus(ALVAC)vaccine expressing human carcinoembryonic antigen and the B7.1co-stimulatory molecule[J].Cancer Immunol Immunother,2000,49(9):504-514.
• [7]Schulze T,Kemmner W,Weitz J,et al.Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases:results of a prospective randomized trial[J].Cancer Immunol Immunother,2009,58(1):61-69.
• [8]Morse MA,Niedzwiecki D,Marshall JL,et al.A randomized phaseⅡstudy of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer[J].Ann Surg,2013,258(6):879-886.
• [9]Andersen R,Donia M,Westergaard MC,et al.Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma[J].Hum Vaccin Immunother,2015,11(12):2790-2795.
• [10]Zhao H,Wang Y,Yu J,et al.Autologous cytokine-induced killer cells improves overall survival of metastatic colorectal cancer patients:results from a phaseⅡclinical trial[J].Clin Colorectal Cancer,2016,15(3):228-235.
• [11]Parkhurst MR,Yang JC,Langan RC,et al.T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis[J].Mol Ther,2011,19(3):620-626.
• [12]Oshima Y,Shimada H,Yajima S,et al.NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer:screening in 1969 patients with various cancers[J].J Gastroenterol,2016,51(1):30-34.
• [13]Dhodapkar MV,Sznol M,Zhao B,et al.Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205[J].Sci Transl Med,2014,6(232):232ra51.
• [14]Robbins PF,Morgan RA,Feldman SA,et al.Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1[J].J Clin Oncol,2011,29(7):917-924.
• [15]Rapoport AP,Stadtmauer EA,Binder-Scholl GK,et al.NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma[J].Nat Med,2015,21(8):914-921.
• [16]Robbins PF,Kassim SH,Tran TL,et al.A pilot trial using lymphocytes genetically engineered with an NYESO-1-reactive T-cell receptor:long-term follow-up and correlates with response[J].Clin Cancer Res,2015,21(5):1019-1027.
• [17]Long YY,Wang Y,Huang QR,et al.Measurement of serum antibodies against NY-ESO-1 by ELISA:A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer[J].Exp Ther Med,2014,8(4):1279-1284.
• [18]Overman MJ.Nivolumab 6 ipilimumab in treatment(tx)of patients(pts)with metastatic colorectal cancer(m CRC)with and without high microsatellite instability(MSI-H):Check Mate-142 interim results[J].J Clin Oncol,2016,34(suppl):abstr 3501.
• [19]Nishino M,Gargano M,Suda M,et al.Optimizing immune-related tumor response assessment:does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab?[J].J Immunother Cancer,2014,2:17.
• [20]Glaudemans AW,Bonanno E,Galli F,et al.In vivo and in vitro evidence that99m Tc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery[J].Eur J Nucl Med Mol Imaging,2014,41(9):1710-1719.
• [21]Chou J,Voong LN,Mortales CL,et al.Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer[J].J Immunother,2012,35(2):131-141.
• [22]Jagadish N,Parashar D,Gupta N,et al.A novel cancer testis antigen target A-kinase anchor protein(AKAP4)for the early diagnosis and immunotherapy of colon cancer[J].Oncoimmunology,2016,5(2):e1078965.
• [23]Katz SC,Burga RA,Mc Cormack E,et al.PhaseⅠhepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+liver metastases[J].Clin Cancer Res,2015,21(14):3149-3159.
• [24]Topalian SL,Hodi FS,Brahmer JR,et al.Safety,activity,and immune correlates of anti-PD-1 antibody in cancer[J].N Engl J Med,2012,366(26):2443-2454.
• [25]Droeser RA,Hirt C,Viehl CT et al.Clinical impact of programmed cell death ligand 1 expression in colorectal cancer[J].Eur J Cancer,2013,49(9):2233-2242.
• [26]Heinimann K.Toward a molecular classification of colorectal cancer:the role of microsatellite instability status[J].Front Oncol,2013,3:272.
• [27]Brahmer JR,Drake CG,Wollner I,et al.PhaseⅠstudy of single-agent anti-programmed death-1(MDX-1106)in refractory solid tumors:safety,clinical activity,pharmacodynamics,and immunologic correlates[J].J Clin Oncol,2010,28(19):3167-3175.
• [28]Lipson EJ,Sharfman WH,Drake CG,et al.Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody[J].Clin Cancer Res,2013,19(2):462-468.
• [29]Le DT.Programmed death-1 blockade in mismatch repair deficient colorectal cancer[J].J Clin Oncol,2016,34(suppl):abstr 103.
• [30]Johanna C.Clinical activity and safety of cobimetinib(cobi)and atezolizumab in colorectal cancer(CRC)[J].J Clin Oncol,2016,34(suppl):abstr 3502.
• [31]Seow HF,Yip WK,Fifis T.Advances in targeted and immunobased therapies for colorectal cancer in the genomic era[J].Onco Targets Ther,2016,9:1899-1920.
• [32]Fong Y,Kim T,Bhargava A,et al.A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer[J].Mol Ther,2009,17(2):389-394.
• [33]Kim RD,Azad NS,Morse M,et al.A phase 2 study of NEO-102(ensituximab),a novel chimeric monoclonal antibody,in adult patients(pts)with unresectable,metastatic colorectal cancer(m CRC)[J].J Clin Oncol,2016,34(suppl):abstr 3080.
• [34]Wolchok JD,Hoos A,O'Day S,et al.Guidelines for the evaluation of immune therapy activity in solid tumors:immune-related response criteria[J].Clin Cancer Res,2009,15(23):7412-7420.
• [35]Nishino M,Giobbie-Hurder A,Gargano M,et al.Developing a common language for tumor response to immunotherapy:immune-related response criteria using unidimensional measurements[J].Clin Cancer Res,2013,19(14):3936-3943.
• [36]Nishino M,Jagannathan JP,Krajewski KM,et al.Personalized tumor response assessment in the era of molecular medicine:cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST[J].Am J Roentgenol,2012,198(4):737-745.
• [37]Okada H,Weller M,Huang R,et al.Immunotherapy response assessment in neuro-oncology:a report of the RANO working group[J].Lancet Oncol,2015,16(15):e534-542.
• [38]Namavari M,Chang YF,Kusler B,et al.Synthesis of 2'-deoxy-2'-[18F]fluoro-9-beta-D-arabinofuranosylguanine:a novel agent for imaging T-cell activation with PET[J].Mol Imaging Biol,2011,13(5):812-818.
• [39]Radu CG,Shu CJ,Nair-Gill E,et al.Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new[18F]-labeled 2'-deoxycytidine analog[J].Nat Med,2008,14(7):783-788.
• [40]Yaghoubi SS,Jensen MC,Satyamurthy N,et al.Noninvasive detection of therapeutic cytolytic T cells with 18FFHBG PET in a patient with glioma[J].Nat Clin Pract Oncol,2009,6(1):53-58.
• [41]den Hollander MW,Bensch F,Glaudemans AW,et al.TGF-beta antibody uptake in recurrent high-grade glioma imaged with89Zr-fresolimumab PET[J].J Nucl Med,2015,56(9):1310-1314.
• [42]Iv M,Telischak N,Feng D,et al.Clinical applications of iron oxide nanoparticles for magnetic resonance imaging of brain tumors[J].Nanomedicine,2015,10(6):993-1018.
• [43]Lamberts LE,Williams SP,Terwisscha van Scheltinga AG,et al.Antibody positron emission tomography imaging in anticancer drug development[J].J Clin Oncol,2015,33(13):1491-1504.
• [44]Galon J,Costes A,Sanchez-Cabo F,et al.Type,density,and location of immune cells within human colorectal tumors predict clinical outcome[J].Science,2006,313(5795):1960-1964.
• [45]Kirilovsky A,Marliot F,El Sissy C,et al.Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients[J].Int Immunol,2016,28(8):373-382.
• [46]Bibeau F.Validation of the Immunoscore(IM)as a prognostic marker in stageⅠ/Ⅱ/Ⅲcolon cancer:Results of a worldwide consortium-based analysis of 1,336patients[J].J Clin Oncol,2016,34(suppl):abstr3500.
• [47]Liu B,Parsons R,Papadopoulos N,et al.Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients[J].Nat Med,1996,2:169-174.
• [48]Kinzler KW,Vogelstein B.Lessons from hereditary colorectal cancer[J].Cell,1996,87(2):159-170.
• [49]Llosa NJ,Cruise M,Tam A,et al.The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints[J].Cancer Discov,2015,5(1):43-51.
• [50]Lawrence MS,Stojanov P,Polak P,et al.Mutational heterogeneity in cancer and the search for new cancer-associated genes[J].Nature,2013,499(7457):214-218.
• [51]Rizvi NA,Hellmann MD,Snyder A,et al.Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J].Science,2015,348(6230):124-128.
• [52]Lipson EJ,Forde PM,Hammers HJ,et al.Antagonists of PD-1 and PD-L1 in cancer treatment[J].Semin Oncol,2015,42(4):587-600.
• [53]Sunshine J,Taube JM.PD-1/PD-L1 inhibitors[J].Curr Opin Pharmacol,2015,23:32-38.
• [54]Motzer RJ,Rini BI,Mc Dermott DF,et al.Nivolumab for metastatic renal cell carcinoma:results of a randomized phaseⅡtrial[J].J Clin Oncol,2015,33(13):1430-1437.
• [55]Taube JM,Klein A,Brahmer JR,et al.Association of PD-1,PD-1 ligands,and other features of the tumor immune microenvironment with response to anti PD-1 therapy[J].Clin Cancer Res,2014,20(19):5064-5074.