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基于免疫检查点PD-1的肿瘤免疫耐药机制及耐药后再治疗的策略

黎钰欣, 金风

黎钰欣, 金风. 基于免疫检查点PD-1的肿瘤免疫耐药机制及耐药后再治疗的策略[J]. 肿瘤防治研究, 2022, 49(6): 546-551. DOI: 10.3971/j.issn.1000-8578.2022.21.1296
引用本文: 黎钰欣, 金风. 基于免疫检查点PD-1的肿瘤免疫耐药机制及耐药后再治疗的策略[J]. 肿瘤防治研究, 2022, 49(6): 546-551. DOI: 10.3971/j.issn.1000-8578.2022.21.1296
LI Yuxin, JIN Feng. Immune Checkpoint PD-1-based Mechanisms of Tumor Immune Resistance and Strategies for Re-treatment After Drug Resistance[J]. Cancer Research on Prevention and Treatment, 2022, 49(6): 546-551. DOI: 10.3971/j.issn.1000-8578.2022.21.1296
Citation: LI Yuxin, JIN Feng. Immune Checkpoint PD-1-based Mechanisms of Tumor Immune Resistance and Strategies for Re-treatment After Drug Resistance[J]. Cancer Research on Prevention and Treatment, 2022, 49(6): 546-551. DOI: 10.3971/j.issn.1000-8578.2022.21.1296

基于免疫检查点PD-1的肿瘤免疫耐药机制及耐药后再治疗的策略

基金项目: 

国家自然科学基金 82060556

贵州省科技计划 [2018]2755

贵州省卫生健康委科学技术基金 gzwkj2021-049

贵州省卫生健康委科学技术基金 gzwki2021-050

详细信息
    作者简介:

    黎钰欣(1997-),女,硕士在读,医师,主要从事头颈肿瘤放射治疗

    金风   二级教授,主任医师, 博士生导师,享受国务院特殊津贴专家,省管专家,国内著名头颈肿瘤专家,省级“巾帼建功标兵”。任中国抗癌协会理事、中国临床肿瘤学会理事、中国抗癌协会鼻咽癌专业委员会常委、中国抗癌协会放射治疗专业委员会常委、中华医学会放射肿瘤治疗学分会头颈肿瘤学组副组长、中国医师协会放射治疗医师分会常委、中国抗癌协会神经肿瘤专委会常委等。贵州省抗癌协会副理事长兼秘书长、贵州省抗癌协会鼻咽癌专业委员会主任委员。主持国家级、省级重大专项子课题、省市级科研项目30多项,研究成果分别荣获中华医学会科技三等奖、贵州省科技成果转化二等奖、省科学技术进步三等奖。发表论文百余篇,其中SCI、中华及核心杂志论文共90余篇。主要研究领域为头颈肿瘤的临床及基础研究,熟练将肿瘤的精确放疗、化疗、分子靶向治疗、免疫治疗运用于临床实践,尤其率领头颈肿瘤团队将时间医学运用于头颈部肿瘤获得“高效低毒”或“等效低毒”的疗效,在国际具有一定影响。参与多中心研究的成果被美国NCCN指南推荐,参与多项国家级鼻咽癌诊疗指南编写

    通信作者:

    金风(1963-),女,本科,主任医师,教授,主要从事头颈肿瘤放射治疗,E-mail: jinf8865@yeah.net

  • 中图分类号: R730.51

Immune Checkpoint PD-1-based Mechanisms of Tumor Immune Resistance and Strategies for Re-treatment After Drug Resistance

Funding: 

National Natural Science Foundation of China 82060556

Science and Technology Project of Guizhou Province [2018]2755

The Science and Technology Fund Project of Guizhou Provincial Health Commission gzwkj2021-049

The Science and Technology Fund Project of Guizhou Provincial Health Commission gzwki2021-050

More Information
  • 摘要:

    免疫治疗被认为是继手术、放疗和化疗后的第四种肿瘤治疗方法。近年来随着对免疫治疗特别是免疫检查点抑制剂研究的深入,PD-1/PD-L1通路抑制剂被批准用于许多癌种的治疗,但由于肿瘤细胞通过多种耐药机制规避免疫应答,免疫检查点阻断存在整体应答率低、原发或继发性耐药等难题。本文阐述了肿瘤免疫耐药的机制,探讨了耐药后再治疗的策略,为提高免疫检查点抑制剂的应答率、降低免疫耐药发生的概率提供理论和临床依据。

     

    Abstract:

    Immunotherapy is considered as the fourth cancer treatment after surgery, radiotherapy and chemotherapy. With the in-depth research on immunotherapy in recent years, especially immuno-checkpoint inhibitors, PD-1/PD-L1 pathway inhibitors have been approved for the treatment of many cancer species. But due to the immune response of tumor cells through multiple drug-resistant mechanisms, immuno-checkpoint blockade has some problems, such as low overall response rate, primary or secondary drug resistance and so on. This paper expounds the mechanism of tumor immune resistance and explores strategies for further treatment after drug resistance, which provides a new theoretical and clinical basis for improving the response rate of immune checkpoint inhibitors and reducing the probability of immune resistance.

     

  • Competing interests: The authors declare that they have no competing interests.
    作者贡献:
    黎钰欣:文献收集整理及论文撰写
    金风:论文选题指导与修改
  • [1]

    Huang C, Li M, Liu B, et al. Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review[J]. Front Oncol, 2021, 11: 642110. doi: 10.3389/fonc.2021.642110

    [2]

    Kong X, Lu P, Liu C, et al. A combination of PD-1/PD-L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)[J]. Mol Med Rep, 2021, 23(5): 362. doi: 10.3892/mmr.2021.12001

    [3]

    Zhang X, Schwartz JC, Guo X, et al. Structural and functional analysis of the costimulatory receptor programmed death-1[J]. Immunity, 2004, 20(3): 337-347. doi: 10.1016/S1074-7613(04)00051-2

    [4]

    Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer[J]. Am J Cancer Res, 2020, 10(3): 727-742.

    [5]

    Wang Z, Wu X. Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker[J]. Cancer Med, 2020, 9(21): 8086-8121. doi: 10.1002/cam4.3410

    [6]

    Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer[J]. Science, 2015, 348(6230): 124-128. doi: 10.1126/science.aaa1348

    [7]

    Patel SA, Minn AJ. Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies[J]. Immunity, 2018, 48(3): 417-433. doi: 10.1016/j.immuni.2018.03.007

    [8]

    Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma[J]. N Engl J Med, 2016, 375(9): 819-829. doi: 10.1056/NEJMoa1604958

    [9]

    Sade-Feldman M, Jiao YJ, Chen JH, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation[J]. Nat Commun, 2017, 8(1): 1136. doi: 10.1038/s41467-017-01062-w

    [10]

    Lei Q, Wang D, Sun K, et al. Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors[J]. Front Cell Dev Biol, 2020, 8: 672. doi: 10.3389/fcell.2020.00672

    [11]

    Sun C, Mezzadra R, Schumacher TN. Regulation and Function of the PD-L1 Checkpoint[J]. Immunity, 2018, 48(3): 434-452. doi: 10.1016/j.immuni.2018.03.014

    [12]

    Zhao S, Ren S, Jiang T, et al. Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer[J]. Cancer Immunol Res, 2019, 7(4): 630-643. doi: 10.1158/2326-6066.CIR-17-0640

    [13]

    Kim K, Park S, Park SY, et al. Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer[J]. Genome Med, 2020, 12(1): 22. doi: 10.1186/s13073-020-00722-9

    [14]

    Zhou J, Tang Z, Gao S, et al. Tumor-Associated Macrophages: Recent Insights and Therapies[J]. Front Oncol, 2020, 10: 188. doi: 10.3389/fonc.2020.00188

    [15]

    Shi T, Ma Y, Yu L, et al. Cancer Immunotherapy: A Focus on the Regulation of Immune Checkpoints[J]. Int J Mol Sci, 2018, 19(5): 1389. doi: 10.3390/ijms19051389

    [16]

    Casadei B, Argnani L, Morigi A, et al. Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma[J]. Cancer Med, 2020, 9(21): 7830-7836. doi: 10.1002/cam4.3262

    [17]

    Suzuki S, Toyoma S, Kawasaki Y, et al. Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma[J]. Medicina (Kaunas), 2021, 57(11): 1151. doi: 10.3390/medicina57111151

    [18]

    Falvo P, Orecchioni S, Hillje R, et al. Cyclophosphamide and Vinorelbine Activate Stem-Like CD8+ T Cells and Improve Anti-PD-1 Efficacy in Triple-Negative Breast Cancer[J]. Cancer Res, 2021, 81(3): 685-697. doi: 10.1158/0008-5472.CAN-20-1818

    [19]

    Wang C, Liu Y, Dong L, et al. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy[J]. Clin Cancer Res, 2021, 27(10): 2782-2791. doi: 10.1158/1078-0432.CCR-21-0133

    [20]

    Ramjiawan RR, Griffioen AW, Duda DG. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?[J]. Angiogenesis, 2017, 20(2): 185-204. doi: 10.1007/s10456-017-9552-y

    [21]

    Lee CH, Shah AY, Rasco D, et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study[J]. Lancet Oncol, 2021, 22(7): 946-958. doi: 10.1016/S1470-2045(21)00241-2

    [22]

    Yang Y, Huang H, Li T, et al. Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma[J]. Front Immunol, 2021, 12: 728750. doi: 10.3389/fimmu.2021.728750

    [23]

    Zhao S, Ren S, Jiang T, et al. Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer[J]. Cancer Immunol Res, 2019, 7(4): 630-643. doi: 10.1158/2326-6066.CIR-17-0640

    [24]

    Yan Z, Ma J, Yao S, et al. Anti-Angiogenic Agent Combined with Anti-PD-1 Immunotherapy Showed Activity in Patients With Classical Hodgkin Lymphoma Who Have Failed Immunotherapy: A Retrospective Case Report Study[J]. Front Immunol, 2021, 12: 727464. doi: 10.3389/fimmu.2021.727464

    [25]

    Chang JY, Mehran RJ, Feng L, et al. Stereotactic ablative radiotherapy for operable stageⅠnon-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery[J]. Lancet Oncol, 2021, 22(10): 1448-1457. doi: 10.1016/S1470-2045(21)00401-0

    [26]

    Benson KRK, Sandhu N, Zhang C, et al. Local Recurrence Outcomes of Colorectal Cancer Oligometastases Treated With Stereotactic Ablative Radiotherapy[J]. Am J Clin Oncol, 2021, 44(11): 559-564. doi: 10.1097/COC.0000000000000864

    [27]

    Yeo ELL, Li YQ, Soo KC, et al. Combinatorial strategies of radiotherapy and immunotherapy in nasopharyngeal carcinoma[J]. Chin Clin Oncol, 2018, 7(2): 15. doi: 10.21037/cco.2018.04.05

    [28]

    Formenti SC, Rudqvist NP, Golden E, et al. Radiotherapy induces responses of lung cancer to CTLA-4 blockade[J]. Nat Med, 2018, 24(12): 1845-1851. doi: 10.1038/s41591-018-0232-2

    [29]

    Leighl NB, Redman MW, Rizvi N, et al. Phase Ⅱ study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage Ⅳ squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)[J]. J Immunother Cancer, 2021, 9(8): e002973. doi: 10.1136/jitc-2021-002973

    [30]

    Kawashima S, Inozume T, Kawazu M, et al. TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment[J]. J Immunother Cancer, 2021, 9(11): e003134.

    [31]

    Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy[J]. J Immunother Cancer, 2020, 8(2): e000957. doi: 10.1136/jitc-2020-000957

    [32]

    Wang J, Sun J, Liu LN, et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy[J]. Nat Med, 2019, 25(4): 656-666. doi: 10.1038/s41591-019-0374-x

    [33]

    Velikova T, Krastev B, Lozenov S, et al. Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure[J]. Int J Mol Sci, 2021, 22(4): 1754. doi: 10.3390/ijms22041754

    [34]

    Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients[J]. Science, 2021, 371(6529): 595-602. doi: 10.1126/science.abf3363

    [35]

    Qi Z, Xu Z, Zhang L, et al. Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment[J]. Nat Commun, 2022, 13(1): 182. doi: 10.1038/s41467-021-27833-0

    [36]

    Iwata TN, Sugihara K, Wada T, et al. [Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti-CTLA-4 antibody in a mouse model[J]. PLoS One, 2019, 14(10): e0222280.

    [37]

    Tian X, Zhu Q, Zhang Z. Durable Clinical Response to Immune and Targeted Therapies in an Elderly Man with Synchronous Gastric (HER2+) and Bladder Cancers: Case Report and Literature Review[J]. Onco Targets Ther, 2021, 14: 3701-3708. doi: 10.2147/OTT.S305039

    [38]

    Catenacci DVT, Kang YK, Park H, et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial[J]. Lancet Oncol, 2020, 21(8): 1066-1076. doi: 10.1016/S1470-2045(20)30326-0

    [39]

    Shekarian T, Sivado E, Jallas AC, et al. Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade[J]. Sci Transl Med, 2019, 11(515): eaat5025. doi: 10.1126/scitranslmed.aat5025

    [40]

    Fang DD, Tang Q, Kong Y, et al. MDM2 inhibitor APG-115 exerts potent antitumor activity and synergizes with standard-of-care agents in preclinical acute myeloid leukemia models[J]. Cell Death Discov, 2021, 7(1): 90. doi: 10.1038/s41420-021-00465-5

    [41]

    Cheng Y, Lemke-Miltner CD, Wongpattaraworakul W, et al. In situ immunization of a TLR9 agonist virus-like particle enhances anti-PD1 therapy[J]. J Immunother Cancer, 2020, 8(2): e000940. doi: 10.1136/jitc-2020-000940

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出版历程
  • 收稿日期:  2021-11-08
  • 修回日期:  2022-03-16
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2022-06-24

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