Research progress on influence of clinical drugs on antitumor effect of immune checkpoint inhibitors
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摘要: 尽管免疫检查点抑制剂(ICI)能够显著改善多种实体肿瘤晚期患者的临床预后，但仍有相当一部分患者并不能从ICI治疗中获益。在临床实践中，抗生素、糖皮质激素、质子泵抑制剂和β受体阻滞剂等多种药物能够通过不同机制影响ICI药物的抗肿瘤效果。抗生素及质子泵抑制剂可能通过影响肠道菌群抑制ICI的治疗效果，而β受体阻滞剂则可能通过抑制β肾上腺素受体信号通路增强肿瘤对ICI的治疗敏感性。糖皮质激素对ICI治疗效果的影响可能依赖于其适应证如肿瘤/非肿瘤相关症状及免疫治疗相关副反应。本研究对上述临床药物在ICI治疗中的相关研究进行综述，以期为优化晚期肿瘤患者ICI个体化治疗策略提供理论依据。Abstract: Although immune checkpoint inhibitors (ICI) can significantly improve the clinical prognosis of patients with advanced solid tumors, a considerable number of patients still can't benefit from ICI treatment. In clinical practice, lots of drugs such as antibiotics, glucocorticoids, proton pump inhibitors and β receptor blockers can affect the antitumor effect of ICI drugs through different mechanisms. Antibiotics and proton pump inhibitors may inhibit the therapeutic effect of ICI by affecting intestinal flora, and β receptor blockers may enhance tumor sensitivity to ICI therapy by inhibiting β adrenoceptor signaling pathway. The effect of glucocorticoid on the therapeutic effect of ICI may depend on its indications, such as tumor/non-tumor related symptoms and immunotherapy related side effects. This study reviewed the related researches on the above clinical drugs in ICI treatment, in order to provide a theoretical basis for optimizing the individualized treatment strategy of ICI in patients with advanced tumors.
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Keywords:
- immune checkpoint inhibitors /
- clinical drugs /
- tumors /
- prognosis /
- intestinal flora
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[1] DOROSHOW D B, BHALLA S, BEASLEY M B, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors[J]. Nat Rev Clin Oncol, 2021, 18(6): 345-362. doi: 10.1038/s41571-021-00473-5
[2] HUSSAIN N, NAEEM M, PINATO D J. Concomitant medications and immune checkpoint inhibitor therapy for cancer: causation or association[J]. Hum Vaccin Immunother, 2021, 17(1): 55-61. doi: 10.1080/21645515.2020.1769398
[3] JENSEN A W P, CARNAZ SIMÕES A M, THOR STRATEN P, et al. Adrenergic signaling in immunotherapy of cancer: friend or foe[J]. Cancers, 2021, 13(3): 394. doi: 10.3390/cancers13030394
[4] LI W Y, DENG X R, CHEN T T. Exploring the modulatory effects of gut microbiota in anti-cancer therapy[J]. Front Oncol, 2021, 11: 644454. doi: 10.3389/fonc.2021.644454
[5] 杨梦雪, 袁满, 童建东, 等. 抗生素在肿瘤发生发展及免疫治疗中的作用[J]. 国际肿瘤学杂志, 2021, 48(1): 48-51. doi: 10.3760/cma.j.cn371439-20200423-00009 [6] 王郁杨, 姜曼, 朱静娟, 等. 肠道微生物与肺癌免疫治疗[J]. 中华肿瘤防治杂志, 2021, 28(14): 1045-1050. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202114002.htm [7] GUVEN D C, ACAR R, YEKEDUZ E, et al. The association between antibiotic use and survival in renal cell carcinoma patients treated with immunotherapy: a multi-center study[J]. Curr Probl Cancer, 2021, 45(6): 100760. doi: 10.1016/j.currproblcancer.2021.100760
[8] MASINI C, BERSELLI A, ROMAGNANI A, et al. Results of an Italian CORE-IMMUNO study: safety and clinical-related biomarkers as predictors of immunotherapy (IT) benefit in real-world treatment of various advanced tumors (ATs)[J]. J Clin Oncol, 2019, 37(15_suppl): e14156. doi: 10.1200/JCO.2019.37.15_suppl.e14156
[9] KADERBHAI C, RICHARD C, FUMET J D, et al. Antibiotic use does not appear to influence response to nivolumab[J]. Anticancer Res, 2017, 37(6): 3195-3200.
[10] GALLI G, TRIULZI T, PROTO C, et al. Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer[J]. Lung Cancer, 2019, 132: 72-78. doi: 10.1016/j.lungcan.2019.04.008
[11] YANG M X, WANG Y, YUAN M, et al. Antibiotic administration shortly before or after immunotherapy initiation is correlated with poor prognosis in solid cancer patients: an up-to-date systematic review and meta-analysis[J]. Int Immunopharmacol, 2020, 88: 106876. doi: 10.1016/j.intimp.2020.106876
[12] 霍庚崴, 宋莹, 陈卫东, 等. 抗生素对免疫检查点抑制剂治疗非小细胞肺癌疗效影响的Meta分析[J]. 中国肿瘤生物治疗杂志, 2021, 28(2): 165-170. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLSW202102010.htm [13] 杨梦雪, 严雪冰, 王颖, 等. 抗生素使用影响免疫检查点抑制剂治疗晚期实体肿瘤效果的临床研究[J]. 国际医药卫生导报, 2021, 27(2): 160-164. doi: 10.3760/cma.j.issn.1007-1245.2021.02.001 [14] HAKOZAKI T, RICHARD C, ELKRIEF A, et al. The gut microbiome associates with immune checkpoint inhibition outcomes in patients with advanced non-small cell lung cancer[J]. Cancer Immunol Res, 2020, 8(10): 1243-1250. doi: 10.1158/2326-6066.CIR-20-0196
[15] MATSON V, FESSLER J, BAO R Y, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients[J]. Science, 2018, 359(6371): 104-108. doi: 10.1126/science.aao3290
[16] CORTELLINI A, TUCCI M, ADAMO V, et al. Integrated analysis of concomitant medications and oncological outcomes from PD-1/PD-L1 checkpoint inhibitors in clinical practice[J]. J Immunother Cancer, 2020, 8(2): e001361. doi: 10.1136/jitc-2020-001361
[17] RIUDAVETS M, MOSQUERA J, GARCIA-CAMPELO R, et al. Immune-related adverse events and corticosteroid use for cancer-related symptoms are associated with efficacy in patients with non-small cell lung cancer receiving anti-PD-(L)1 blockade agents[J]. Front Oncol, 2020, 10: 1677. doi: 10.3389/fonc.2020.01677
[18] THOMPSON L L, KATZNELSON E, LEET D E, et al. Impact of systemic corticosteroids on survival outcomes in immune checkpoint inhibitor-induced gastroenterocolitis[J]. Eur J Cancer, 2021, 142: 143-146. doi: 10.1016/j.ejca.2020.09.022
[19] DE GIGLIO A, MEZQUITA L, AUCLIN E, et al. Impact of intercurrent introduction of steroids on clinical outcomes in advanced non-small-cell lung cancer (NSCLC) patients under immune-checkpoint inhibitors (ICI)[J]. Cancers, 2020, 12(10): 2827. doi: 10.3390/cancers12102827
[20] JOVE M, VILARIÑO N, NADAL E. Impact of baseline steroids on efficacy of programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in patients with advanced non-small cell lung cancer[J]. Transl Lung Cancer Res, 2019, 8(Suppl 4): S364-S368.
[21] MAXWELL R, LUKSIK A S, GARZON-MUVDI T, et al. Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system[J]. Oncoimmunology, 2018, 7(12): e1500108. doi: 10.1080/2162402X.2018.1500108
[22] OKOYE I S, XU L, WALKER J, et al. The glucocorticoids prednisone and dexamethasone differentially modulate T cell function in response to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade[J]. Cancer Immunol Immunother, 2020, 69(8): 1423-1436. doi: 10.1007/s00262-020-02555-2
[23] WANG Y, YANG M X, TAO M Y, et al. Corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving immune checkpoint inhibitor treatment[J]. Int Immunopharmacol, 2021, 99: 108031. doi: 10.1016/j.intimp.2021.108031
[24] HOPKINS A M, KICHENADASSE G, KARAPETIS C S, et al. Concomitant proton pump inhibitor use and survival in urothelial carcinoma treated with atezolizumab[J]. Clin Cancer Res, 2020, 26(20): 5487-5493. doi: 10.1158/1078-0432.CCR-20-1876
[25] HOMICSKO K, RICHTIG G, TUCHMANN F, et al. Proton pump inhibitors negatively impact survival of PD-1 inhibitor based therapies in metastatic melanoma patients[J]. Ann Oncol, 2018, 29: x40.
[26] CHALABI M, CARDONA A, NAGARKAR D R, et al. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials[J]. Ann Oncol, 2020, 31(4): 525-531. doi: 10.1016/j.annonc.2020.01.006
[27] AFZAL M Z, SHIRAI K. What impact do the proton pump inhibitors have on the efficacy of immune check point inhibitors in metastatic malignant melanoma[J]. J Clin Oncol, 2019, 37(Suppl 15): e21040.
[28] TRABOLSI A, WINTER M, RODRIGUEZ E. Proton pump inhibitors and response to immune check-point inhibitors: single center study[J]. J Clin Oncol, 2019, 37(Suppl 15): e14092.
[29] OH M S, GUZNER A, WAINWRIGHT D A, et al. The impact of beta blockers on survival outcomes in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors[J]. Clin Lung Cancer, 2021, 22(1): e57-e62. doi: 10.1016/j.cllc.2020.07.016
[30] KOKOLUS K M, ZHANG Y, SIVIK J M, et al. Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice[J]. Oncoimmunology, 2017, 7(3): e1405205.
[31] GANDHI S, PANDEY M, AMMANNAGARI N, et al. Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors[J]. Immunotherapy, 2020, 12(2): 141-149. doi: 10.2217/imt-2019-0064
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