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2019, 05, v.44;No.222 76-83
肿瘤免疫治疗现状及发展前景
基金项目(Foundation): 国家自然科学基金项目(81860494)
邮箱(Email):
DOI: 10.16112/j.cnki.53-1223/n.2019.05.012
摘要:

由于先天免疫系统和后天免疫系统在免疫监视和免疫防御中发挥着决定性作用.因此,利用免疫系统治疗癌症是一种非常有前景的方法.免疫治疗是一个快速发展的领域,代表了恶性肿瘤治疗的范式转变,它提供了一种超越外科手术、常规化疗和放疗的新型治疗方法.如今,癌症免疫治疗方法主要包括免疫检查点封锁、嵌合抗原受体(CAR)T细胞过继免疫、治疗性肿瘤疫苗等.研究目标不仅是针对激活肿瘤的免疫系统,还要考虑目前治疗所存在的阻碍.这些治疗方法解决了部分在血液瘤以及实体瘤难以攻克的问题,为接下来的肿瘤治疗打下基础.本综述主要集中论述当前癌症免疫治疗的方法及现状、当前困境及突破,展现了对肿瘤免疫学方面的基本认识并对其进行展望.

Abstract:

As innate immune system and acquired immune system play a decisive role in immune surveillance and defense, using the immune system to treat cancer is a very promising method. Immunotherapy is a rapidly growing field and represents a paradigm shift in the treatment of malignancies as it offers a new therapeutic approach beyond surgery, conventional chemotherapy, and radiation treatment. Nowadays, immunotherapy for cancer mainly includes blockade of immune checkpoints, adoptive immunization of chimeric antigen receptor(CAR) T cells, therapeutic cancer vaccines and so on. The objective of this study is not only to activate the immune system of tumors, but also to consider the obstacles caused by current treatment. These treatments solve some of the problems that are difficult to overcome in hematomas and solid tumors, and lay the foundation for the next treatment of tumors. This review focuses on current methods and current status of tumor immunotherapy, current difficulties and breakthroughs, showing the basic understanding of cancer immunology and its prospects.

参考文献

[1] Wei S C,Duffy C R,Allison J P.Fundamental mechanisms of immune checkpoint blockade therapy[J].Cancer discovery,2018,8(9):1069-1086.

[2] Lu Y C,Jia L,Zheng Z,et al.Single-cell transcriptome analysis reveals gene signatures associated with T-cell persistence following adoptive cell therapy[J].Cancer immunology research,2019.

[3] Gross G,Eshhar Z.Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment:counteracting off-tumor toxicities for safe CAR T cell therapy[J].Annual review of pharmacology and toxicology,2016,56:59-83.

[4] Pardoll D M.The blockade of immune checkpoints in cancer immunotherapy[J].Nature Reviews Cancer,2012,12(4):252-264.

[5] Baumeister S H,Freeman G J,Dranoff G,et al.Coinhibitory pathways in immunotherapy for cancer[J].Annual review of immunology,2016,34:539-573..

[6] Kong B Y,Bolton H,Silveira P A,et al.On the Other Side:Manipulating the Immune Checkpoint Landscape of Dendritic Cells to Enhance Cancer Immunotherapy[J].Frontiers in oncology,2019,9:50.

[7] Song Y,Li Z,Xue W,et al.Predictive biomarkers for PD-1 and PD-L1 immune checkpoint blockade therapy[J].Immunotherapy,2019,11(6):515-529.

[8] Kamphorst A O,Wieland A,Nasti T,et al.Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent[J].Science,2017,355(6332):1423-1427.

[9] Larkin J,Chiarion-Sileni V,Gonzalez R,et al.Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J].New England journal of medicine,2015,373(1):23-34.

[10] Johnson L A,June C H.Driving gene-engineered T cell immunotherapy of cancer[J].Cell research,2017,27(1):38-58.

[11] Zhou H,Luo Y,Zhu S,et al.The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor-T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis[J].BMC cancer,2018,18(1):929.

[12] Sadelain M,Brentjens R,Rivière I.The basic principles of chimeric antigen receptor design[J].Cancer discovery,2013,3(4):388-398.

[13] Zhao Z,Condomines M,van der Stegen S J C,et al.Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells[J].Cancer cell,2015,28(4):415-428.

[14] Li W,Song X,Jin Y,et al.CARTs for Solid Tumors:Feasible or Infeasible?[J].Oncology research and treatment,2017,40(9):540-546.

[15] Pettitt D,Arshad Z,Smith J,et al.CAR-T cells:a systematic review and mixed methods analysis of the clinical trial landscape[J].Molecular Therapy,2018,26(2):342-353.

[16] Chmielewski M,Abken H.TRUCKs:the fourth generation of CARs[J].Expert opinion on biological therapy,2015,15(8):1145-1154.

[17] Van Schandevyl S,Kerre T.Chimeric antigen receptor T-cell therapy:design improvements and therapeutic strategies in cancer treatment[J].Acta Clinica Belgica,2018,15:1-7.

[18] Zhen A,Peterson C W,Carrillo M A,et al.Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS[J].PLoS pathogens,2017,13(12):e1006753.

[19] Jackson H J,Rafiq S,Brentjens R J.Driving CAR T-cells forward[J].Nature reviews Clinical oncology,2016,13(6):370.

[20] Kawalekar O U,O’Connor R S,Fraietta J A,et al.Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells[J].Immunity,2016,44(2):380-390.

[21] Allahverdiyev A,Tari G,Bagirova M,et al.Current Approaches in Development of Immunotherapeutic Vaccines for Breast Cancer[J].Journal of breast cancer,2018,21(4):343-353.

[22] Melero I,Gaudernack G,Gerritsen W,et al.Therapeutic vaccines for cancer:an overview of clinical trials[J].Nature reviews Clinical oncology,2014,11(9):509.

[23] Pilla L,Ferrone S,Maccalli C.Methods for improving the immunogenicity and efficacy of cancer vaccines[J].Expert opinion on biological therapy,2018,18(7):765-784.

[24] Schlom J,Gulley J L.Vaccines as an integral component of cancer immunotherapy[J].Jama,2018,320(21):2195-2196.

[25] Zhu G,Mei L,Vishwasrao H D,et al.Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy[J].Nature communications,2017,8(1):1482.

[26] Schumacher T N,Schreiber R D.Neoantigens in cancer immunotherapy[J].Science,2015,348(6230):69-74.

[27] Vormehr M,Diken M,Boegel S,et al.Mutanome directed cancer immunotherapy[J].Current Opinion in Immunology,2016,39:14-22.

[28] Van Allen E M,Miao D,Schilling B,et al.Genomic correlates of response to CTLA-4 blockade in metastatic melanoma[J].Science,2015,350(6257):207-211.

[29] Rizvi N A,Hellmann M D,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.

[30] Le D T,Uram J N,Wang H,et al.PD-1 blockade in tumors with mismatch-repair deficiency[J].New England Journal of Medicine,2015,372(26):2509-2520.

[31] Evans R A,Diamond M S,Rech A J,et al.Lack of immunoediting in murine pancreatic cancer reversed with neoantigen[J].JCI insight,2016,1(14):e88328.

[32] Buettner M J,Shah S R,Saeui C T,et al.Improving immunotherapy through glycodesign[J].Frontiers in immunology,2018,9:1-29.

[33] Shimizu T,Lila A S A,Kawaguchi Y,et al.A novel platform for cancer vaccines:antigen-selective delivery to splenic marginal zone B cells via repeated injections of PEGylated liposomes[J].The Journal of Immunology,2018,201(10):2969-2976.

[34] Jaros?awski S,Toumi M.Sipuleucel-T (Provenge?)—Autopsy of an innovative paradigm change in cancer treatment:why a single-product biotech company failed to capitalize on its breakthrough invention[J].BioDrugs,2015,29(5):301-307.

[35] Ott P A,Hu Z,Keskin D B,et al.Corrigendum:an immunogenic personal neoantigen vaccine for patients with melanoma[J].Nature,2018,555(7696):402.

[36] Hanahan D,Weinberg R A.Hallmarks of cancer:the next generation[J].cell,2011,144(5):646-674.

[37] Sakurai D,Uchida R,Ihara F,et al.Immunosuppressive property of submandibular lymph nodes in patients with head and neck tumors:differential distribution of regulatory T cells[J].BMC research notes,2018,11(1):479.

[38] Vinay D S,Ryan E P,Pawelec G,et al.Immune evasion in cancer:Mechanistic basis and therapeutic strategies[C]//Seminars in cancer biology.Academic Press,2015,35:S185-S198.

[39] Wu S G,Liu Y N,Tsai M F,et al.The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients[J].Oncotarget,2016,7(11):12404.

[40] Jafarzadeh A,Nemati M,Khorramdelazad H,et al.Immunomodulatory properties of cimetidine:Its therapeutic potentials for treatment of immune-related diseases[J].International immunopharmacology,2019,70:156-166.

[41] Highfill S L,Cui Y,Giles A J,et al.Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy[J].Science translational medicine,2014,6(237):237-267.

[42] Deng G.Tumor-infiltrating regulatory T cells:origins and features[J].American journal of clinical and experimental immunology,2018,7(5):81-87.

[43] Barrow A D,Colonna M.Innate lymphoid cell sensing of tissue vitality[J].Current opinion in immunology,2019,56:82-93.

[44] Gao S,Yang D,Fang Y,et al.Engineering nanoparticles for targeted remodeling of the tumor microenvironment to improve cancer immunotherapy[J].Theranostics,2019,9(1):126-151.

[45] Tosolini M,Kirilovsky A,Mlecnik B,et al.Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1,th2,treg,th17) in patients with colorectal cancer[J].Cancer research,2011,71(4):1263-1271.

[46] Nagarsheth N,Wicha M S,Zou W.Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy[J].Nature Reviews Immunology,2017,17(9):559.

[47] Dalgleish A G.Rationale for combining immunotherapy with chemotherapy[J].Immunotherapy,2015,7(3):309-316.

[48] Wargo J A,Reuben A,Cooper Z A,et al.Immune effects of chemotherapy,radiation,and targeted therapy and opportunities for combination with immunotherapy[C]//Seminars in oncology.WB Saunders,2015,42(4):601-616.

[49] Sharabi A B,Lim M,DeWeese T L,et al.Radiation and checkpoint blockade immunotherapy:radiosensitisation and potential mechanisms of synergy[J].The lancet oncology,2015,16(13):e498-e509.

[50] Shahabi V,Postow M A,Tuck D,et al.Immune-priming of the tumor microenvironment by radiotherapy:rationale for combination with immunotherapy to improve anticancer efficacy[J].American journal of clinical oncology,2015,38(1):90-97.

[51] Teng F,Kong L,Meng X,et al.Radiotherapy combined with immune checkpoint blockade immunotherapy:achievements and challenges[J].Cancer letters,2015,365(1):23-29.

[52] Hughes P E,Caenepeel S,Wu L C.Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer[J].Trends in immunology,2016,37(7):462-476.

[53] Dunn J,Rao S.Epigenetics and immunotherapy:the current state of play[J].Molecular immunology,2017,87:227-239.

[54] Ledford H.Cocktails for cancer with a measure of immunotherapy[J].Nature News,2016,532(7598):162-164.

基本信息:

DOI:10.16112/j.cnki.53-1223/n.2019.05.012

中图分类号:R730.51

引用信息:

[1]李芳芳,郑尚永.肿瘤免疫治疗现状及发展前景[J].昆明理工大学学报(自然科学版),2019,44(05):76-83.DOI:10.16112/j.cnki.53-1223/n.2019.05.012.

基金信息:

国家自然科学基金项目(81860494)

投稿时间:

2018-12-29

投稿日期(年):

2018

终审时间:

2019-11-08

终审日期(年):

2019

审稿周期(年):

2

发布时间:

2019-10-15

出版时间:

2019-10-15

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