恶性肿瘤免疫治疗的研究进展

doi:10.11904/j.issn.1002-3070.2026.01.011

摘要/Abstract

摘要： 在全球范围内,高发病率及致死率的恶性肿瘤严重影响人类健康。恶性肿瘤的免疫治疗现已成为继手术、放疗、化疗之后的第四种重要治疗手段。目前已开发应用于临床的肿瘤免疫治疗主要包括:免疫检查点抑制剂、肿瘤疫苗、过继细胞免疫治疗以及双特异性抗体疗法。免疫治疗正进入多模态协同时代,通过与生物工程、人工智能及纳米递送技术等的联合应用,最终实现从“疾病治疗”到“精准调控”的范式转变。本文归纳了不同肿瘤免疫治疗的特点、局限性及临床研究进展,系统阐述了肿瘤免疫治疗的基本原理,分析了肿瘤免疫治疗在应对肿瘤免疫逃逸、克服耐药性及降低毒副作用等方面的进展与挑战,并展望了通过多学科技术融合实现个性化精准治疗的发展方向。

关键词: 免疫治疗, 肿瘤免疫, 免疫检查点抑制剂, 肿瘤疫苗, 过继细胞免疫治疗

Abstract: Globally,malignant tumors with high incidence and mortality seriously affect human health.Immunotherapy for malignant tumors has now become the fourth important treatment method after surgery,radiotherapy,and chemotherapy.Currently,tumor immunotherapies that have been developed for clinical application mainly include immune checkpoint inhibitors,tumor vaccines,adoptive cellular immunotherapy,and bispecific antibodies.Immunotherapy is entering an era of multimodal synergy,where it is combined with bioengineering,artificial intelligence,and nanotechnology delivery to ultimately achieve a paradigm shift from "disease treatment" to "precise modulation." This review summarizes the characteristics,limitations,and clinical research progress of different tumor immunotherapies,systematically expounds on the basic principles of tumor immunotherapy,analyzes the progress and challenges of tumor immunotherapy in addressing tumor immune escape,overcoming drug resistance,and reducing toxic side effects,and looks forward to the development direction of personalized precision therapy through multidisciplinary technological integration.

Key words: immunotherapy, tumor immunity, immune checkpoint inhibitors, cancer vaccines, adoptive cellular immunotherapy

中图分类号:

R730.51

张佳宁, 张颐, 张晓莲, 李海英, 王大庆. 恶性肿瘤免疫治疗的研究进展[J]. 实用肿瘤学杂志, 2026, 40(1): 75-82.

ZHANG Jianing, ZHANG Yi, ZHANG Xiaolian, LI Haiying, WANG Daqing. Research progress in immunotherapy for malignant tumors[J]. Journal of Practical Oncology, 2026, 40(1): 75-82.

参考文献

1 张希,杨雷,刘硕,等. 2022年全球恶性肿瘤统计报告解读[J]. 中华肿瘤杂志,2024,46(07):710-721.
2 Krenz B,Lee J,Kannan T,et al.Immune evasion:An imperative and consequence of MYC deregulation[J].Mol Oncol,2024,18(10):2338-2355.
3 Nenclares P,Rullan A,Tam K,et al.Introducing checkpoint inhibitors into the curative setting of head and neck cancers:lessons learned,future considerations[J].Am Soc Clin Oncol Educ Book,2022,42:1-16.
4 Qin S,Chan SL,Gu S,et al.Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma(CARES-310):a randomised,open-label,international phase 3 study[J].Lancet,2023,402(10408):1133-1146.
5 Ghisoni E,Wicky A,Bouchaab H,et al.Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors:An overlooked aspect in immunotherapy[J].Eur J Cancer,2021,149:153-164.
6 Jung YS,Park JI.Wnt signaling in cancer:therapeutic targeting of wnt signaling beyond β-catenin and the destruction complex[J].Exp Mol Med,2020,52(2):183-191.
7 Geoerger B,Bergeron C,Gore L,et al.Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma[J].Eur J Cancer,2017,86:358-363.
8 Brahmer J,Reckamp KL,Baas P,et al.Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J].N Engl J Med,2015,373(2):123-135.
9 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.
10 Motzer RJ,Escudier B,McDermott DF,et al.Nivolumab versus everolimus in advanced renal-cell carcinoma[J].N Engl J Med,2015,373(19):1803-1813.
11 El-Khoueiry AB,Sangro B,Yau T,et al.Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492-2502.
12 Chen R,Zinzani PL,Fanale MA,et al.Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic hodgkin lymphoma[J].J Clin Oncol,2017,35(19):2125-2132.
13 Fuchs CS,Doi T,Jang RW,et al.Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer:phase 2 clinical KEYNOTE-059 trial[J].JAMA Oncol,2018,4(5):e180013.
14 Rosenberg JE,Hoffman JC,Powles T,et al.Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy:a single-arm,multicentre,phase 2 trial[J].Lancet,2016,387(10031):1909-1920.
15 Rittmeyer A,Barlesi F,Waterkamp D,et al.Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer(OAK):a phase 3,open-label,multicentre randomised controlled trial[J].Lancet,2017,389(10066):255-265.
16 Kaufman HL,Russell J,Hamid O,et al.Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma:a multicentre,single-group,open-label,phase 2 trial[J].Lancet Oncol,2016,17(10):1374-1385.
17 Powles T,O′Donnell PH,Massard C,et al.Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma:updated results from a phase 1/2 open-label study[J].JAMA Oncol,2017,3(9):e172411.
18 Antonia SJ,Villegas A,Daniel D,et al.Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC[J].N Engl J Med,2018,379(24):2342-2350.
19 Paik J.Nivolumab plus relatlimab:first approval[J].Drugs,2022,82(8):925-931.
20 Zheng M.Sex-differential responses to immune checkpoint inhibitors across the disease continuum unified by tumor mutational burden[J].Semin Oncol,2025,52(6):152414.
21 Zgura A,Chipuc S,Bacalbasa N,et al.Evaluating tumour mutational burden as a key biomarker in personalized cancer immunotherapy:a pan-cancer systematic review[J].Cancers(Basel),2025,17(3):480.
22 Wilbur HC,Le DT,Agarwal P.Immunotherapy of MSI cancer:facts and hopes[J].Clin Cancer Res,2024,30(8):1438-1447.
23 Knetki-Wróblewska M,Wojas-Krawczyk K,Krawczyk P,et al.Emerging insights into STK11,KEAP1 and KRAS mutations:implications for immunotherapy in patients with advanced non-small cell lung cancer[J].Transl Lung Cancer Res,2024,13(12):3718-3730.
24 Skoulidis F,Araujo HA,Do MT,et al.CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors[J].Nature,2024,635(8038):462-471.
25 Liang Y,Maeda O,Kondo C,et al.Effects of KRAS,STK11,KEAP1,and TP53 mutations on the clinical outcomes of immune checkpoint inhibitors among patients with lung adenocarcinoma[J].PLoS One,2024,19(7):e0307580.
26 Ma W,Shi Q,Su X,et al.Carcinoembryonic antigen as a predictor of treatment outcomes in cancer patients receiving immune checkpoint inhibitors[J].Ann Med,2025,57(1):2531255.
27 Eiman L,Moazzam K,Anjum S,et al.Gut dysbiosis in cancer immunotherapy:microbiota-mediated resistance and emerging treatments[J].Front Immunol,2025,16:1575452.
28 Chen J,Gao Y,Chen Y,et al.Identification and validation of intratumoral microbiome associated with sensitization to immune checkpoint inhibitors[J].Cell Rep Med,2025,6(9):102306.
29 Zhang L,Zhou DD,Feng J,et al.Intestinal fungal signatures and their impact on immune checkpoint inhibitor efficacy:a multi-cohort meta-analysis[J].NPJ Biofilms Microbiomes,2025,11(1):188.
30 Szóstak N,Handschuh L,Samelak-Czajka A,et al.Host factors associated with gut mycobiome structure[J].mSystems,2023,8(2):e0098622.
31 Hu M,Zhu X,Huang X,et al.Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype[J].Cell Rep,2025,44(5):115589.
32 Sobhani N,Scaggiante B,Morris R,et al.Therapeutic cancer vaccines:From biological mechanisms and engineering to ongoing clinical trials[J].Cancer Treat Rev,2022,109:102429.
33 Tang Y,Yi X,Ai J.mRNA vaccines for prostate cancer:a novel promising immunotherapy[J].Biochim Biophys Acta Rev Cancer,2025,1880(3):189333.
34 Chen C,Fan G,Li P,et al.Comparative study on the efficacy of low-dose and full-dose BCG bladder perfusion therapy[J].Clin Transl Oncol,2025,27(5):2174-2190.
35 Davidson SK,Dedeilia A,Lawless A,et al.Genetic factors associated with clinical response in melanoma patients treated with talimogene laherparapvec:a single-Institution retrospective analysis[J].Ann Surg Oncol,2025,32(1):482-494.
36 Ferrucci PF,Pala L,Conforti F,et al.Talimogene laherparepvec(T-VEC):an intralesional cancer immunotherapy for advanced melanoma[J].Cancers(Basel),2021,13(6):1383.
37 Jain AG,Talati C,Pinilla-Ibarz J.Galinpepimut-S(GPS):an investigational agent for the treatment of acute myeloid leukemia[J].Expert Opin Investig Drugs,2021,30(6):595-601.
38 Trimble CL,Morrow MP,Kraynyak KA,et al.Safety,efficacy,and immunogenicity of VGX-3100,a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3:a randomised,double-blind,placebo-controlled phase 2b trial[J].Lancet,2015,386(10008):2078-2088.
39 Deng Z,Tian Y,Song J,et al.mRNA vaccines:the dawn of a new era of cancer immunotherapy[J].Front Immunol,2022,13:887125.
40 Rojas LA,Sethna Z,Soares KC,et al.Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer[J].Nature,2023,618(7963):144-150.
41 Handy CE,Antonarakis ES.Sipuleucel-T for the treatment of prostate cancer:novel insights and future directions[J].Future Oncol,2018,14(10):907-917.
42 Talimogene laherparepvec for melanoma[J].Aust Prescr,2017,40(1):38-39.
43 Butterfield LH,Ribas A,Dissette VB,et al.Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma[J].Clin Cancer Res,2003,9(3):998-1008.
44 Van Tendeloo VF,Van de Velde A,Van Driessche A,et al.Induction of complete and molecular remissions in acute myeloid leukemia by Wilms′ tumor 1 antigen-targeted dendritic cell vaccination[J].Proc Natl Acad Sci U S A,2010,107(31):13824-13829.
45 Steele MM,Jaiswal A,Delclaux I,et al.T cell egress via lymphatic vessels is tuned by antigen encounter and limits tumor control[J].Nat Immunol,2023,24(4):664-675.
46 刘宝瑞.实体肿瘤免疫治疗的关键问题与对策[J].中国肿瘤生物治疗杂志,2017,24(06):575-580.
47 Gibbs C,So JY,Ahad A,et al.CXCL14 attenuates triple-negative breast cancer progression by regulating immune profiles of the tumor microenvironment in a T cell-dependent manner[J].Int J Mol Sci,2022,23(16):9314.
48 Gorchs L,Oosthoek M,Yucel-Lindberg T,et al.Chemokine receptor expression on T cells is modulated by CAFs and chemokines affect the spatial distribution of T cells in pancreatic tumors[J].Cancers(Basel),2022,14(15):3826.
49 Maude SL,Laetsch TW,Buechner J,et al.Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia[J].N Engl J Med,2018,378(5):439-448.
50 Locke FL,Ghobadi A,Jacobson CA,et al.Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma(ZUMA-1):a single-arm,multicentre,phase 1-2 trial[J].Lancet Oncol,2019,20(1):31-42.
51 Wang M,Munoz J,Goy A,et al.KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma[J].N Engl J Med,2020,382(14):1331-1342.
52 Abramson JS,Palomba ML,Gordon LI,et al.Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas(TRANSCEND NHL 001):a multicentre seamless design study[J].Lancet,2020,396(10254):839-852.
53 Munshi NC,Anderson LD,Shah N,et al.Idecabtagene vicleucel in relapsed and refractory multiple myeloma[J].N Engl J Med,2021,384(8):705-716.
54 Berdeja JG,Madduri D,Usmani SZ,et al.Ciltacabtagene autoleucel,a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma(CARTITUDE-1):a phase 1b/2 open-label study[J].Lancet,2021,398(10297):314-324.
55 Tsimberidou AM,Van Morris K,Vo HH,et al.T-cell receptor-based therapy:an innovative therapeutic approach for solid tumors[J].J Hematol Oncol,2021,14(1):102.
56 Knafler G,Ho AL,Moore KN,et al.Melanoma-associated antigen A4:a cancer/testis antigen as a target for adoptive T-cell receptor T-cell therapy[J].Cancer Treat Rev,2025,134:102891.
57 Lv M,Shi D,Zhao X,et al.IGFBP2 up-regulation by EBV via TGF-β signaling:a key mechanism in nasopharyngeal carcinoma progression[J].Virus Genes,2025,61(5):562-573.
58 Stevanovic′S,Helman SR,Wunderlich JR,et al.A Phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers[J].Clin Cancer Res,2019,25(5):1486-1493.
59 Lee HJ,Kim YA,Sim CK,et al.Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer[J].Oncotarget,2017,8(69):113345-113359.
60 Wu W,Pu Y,Shi J.Nanomedicine-enabled chemotherapy-based synergetic cancer treatments[J].J Nanobiotechnology,2022,20(1):4.
61 Wegmann R,Bankel L,Festl Y,et al.Molecular and functional landscape of malignant serous effusions for precision oncology[J].Nat Commun,2024,15(1):8544.
62 Zhou Y,Zhang C,Wang Y,et al.The safe Laccase@ZIF-8-prodrug system with GSH redox cycle for effective targeted cancer therapy with low off-target toxicity[J].Colloids Surf B Biointerfaces,2022,220:112853.
63 Gupta A,Bajaj S,Nema P,et al.Potential of AI and ML in oncology research including diagnosis,treatment and future directions:a comprehensive prospective[J].Comput Biol Med,2025,189:109918.

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