Research progress on radiotherapy combined with immune checkpoint inhibitor in the treatment of non-small cell lung cancer
Jin Jianan1, Xu Yujin2, Chen Mengyuan2, Chen Ming2
1The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China; 2Department of Cancer andBasic Medicine, Chinese Academy of Sciences;Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Hangzhou 310022, China
Abstract：The emergence of immune checkpoint inhibitors (ICI) provides a novel method for the treatment of non-small cell lung cancer (NSCLC). However, the limitation of ICI alone prompts clinicians to explore the feasibility of radiotherapy combined with ICI. Recent studies on this combined therapy have preliminarily revealed its significant prospects for changing the treatment system of NSCLC. From the perspective of the mechanism of combined therapy, this study reviewed the basic research on this combined therapy and the clinical progress on different radiotherapy combined with ICI.
Jin Jianan,Xu Yujin,Chen Mengyuan et al. Research progress on radiotherapy combined with immune checkpoint inhibitor in the treatment of non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2020, 29(6): 477-481.
[1] 陈万青, 李贺, 孙可欣, 等. 2014年中国恶性肿瘤发病和死亡分析[J]. 中华肿瘤杂志, 2018, 40(1):5-13. DOI:10.3760/cma.j.issn.0253-3766.2018.01.002. [2] Reck M, Rabe KF. Precision diagnosis and treatment for advanced non-small-cell lung cancer[J]. N Engl J Med, 2017, 377(9):849-861. DOI:10.1056/NEJMra1703413. [3] Saadeddin A. Radiotherapy for NSCLC:review of conventional and new treatment techniques[J]. J Infect Public Health, 2012, 5(Suppl 1):s45-s49. DOI:10.1016/j.jiph. 2012.09.002. [4] Janakiram M, Pareek V, Cheng H, etal. Immune checkpoint blockade inhuman cancer therapy:lung cancerand hematologic malignancies[J].Immunotherapy, 2016, 8(7):809-819. DOI:10.2217/imt-2016-0001. [5] 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. DOI:10.1056/NEJMoa1504627. [6] Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer[J]. N Engl J Med, 2015, 373(17):1627-1639. DOI:10.1056/NEJMoa1507643. [7] 袁梦, 门玉, 惠周光. NSCLC放疗联合免疫治疗研究进展[J]. 中华放射肿瘤学杂志, 2018, 27(5):533-537. DOI:10.3760/cma.j.issn.1004-4221.2018.05.020. [8] Abuodeh Y, Venkat P, Kim S. Systematic review of case reports on the abscopal effect[J]. Curr Probl Cancer, 2016, 40(1):25-37. DOI:10.1016/j.currproblcancer. 2015.10.001. [9] Mole RH. Whole body irradiation;radiobiology or medicine?[J]. Br J Radiol, 1953, 26(305):234-241. DOI:10.1259/0007-1285-26-305-234. [10] Demaria S, Ng B, Devitt ml, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated[J]. Int J Radiat Oncol Biol Phys, 2004, 58(3):862-870. DOI:10.1016/j.ijrobp. 2003.09.012. [11] Britschgi C, Riesterer O, Burger IA, et al. Report of an abscopal effect induced by stereotactic body radiotherapy and nivolumab in a patient with metastatic non-small cell lung cancer[J]. Radiat oncol, 2018, 13(1):102. DOI:10.1186/s13014-018-1049-3. [12] Siva S, Callahan J, MacManus MP, et al. Abscopal[corrected] effects after conventional and stereotactic lung irradiation of non-small-cell lung cancer[J]. J Thorac Oncol, 2013, 8(8):e71-e72. DOI:10.1097/JTO. 0b013e318292c55a. [13] Kroemer G, Galluzzi L, Kepp O, et al. Immunogenic cell death in cancer therapy[J]. Annu Rev Immunol, 2013, 31(1):51-72. DOI:10.1146/annurev-immunol-032712-100008. [14] Frey B, Rubner Y, Kulzer L, et al. Antitumor immune responses induced by ionizing irradiation and further immune stimulation[J]. Cancer Immunol Immunother, 2014, 63(1):29-36. DOI:10.1007/s00262-013-1474-y. [15] Daly ME, Monjazeb AM, Kelly K. Clinical trials integrating immunotherapy and radiation for non-small-cell lung cacncer[J]. J Thoracic Oncol, 2015, 10(12):1685-1693. DOI:10.1097/JTO. 0000000000000686. [16] Vanpouille-Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity[J]. Nat Commun, 2017, 8:15618. DOI:10.1038/ncomms15618. [17] Borghaei H, Smith MR, Campbell KS. Immunotherapy of cancer[J]. Eur J Pharmacol, 2009, 625(1-3):41-54. DOI:10.1016/j.ejphar. 2009.09.067. [18] Gray LH, Conger AD, Ebert M, et al. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy[J]. Br J Radiol, 1953, 26(312):638-648. DOI:10.1259/0007-1285-26-312-638. [19] Wright EA, Howard-Flanders P. The influence of oxygen on the radiosensitivity of mammalian tissues[J]. Acta Radiol, 1957, 48(1):26-32. DOI:10.3109/00016925709170930. [20] Maione F, Giraudo E. Tumor angiogenesis:methods to analyze tumor vasculature and vessel normalization in mouse models of cancer[J]. Methods Mol biol, 2015,1267:349-365. DOI:10.1007/978-1-4939-2297-0_17. [21] Wang Y, Liu Z, Yuan H, et al. The reciprocity between radiotherapy and cancer immunotherapy[J]. Clin Cancer Res, 2019,25(6):1709-1717. DOI:10.1158/1078-0432. CCR-18-2581. [22] Tian L, Goldstein A, Wang H, et al. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming[J]. Nature, 2017, 544(7649):250-254. DOI:10.1038/nature21724. [23] Zheng X, Fang Z, Liu X, et al. Increased vessel perfusion predicts the efficacy of immune checkpoint blockade[J]. J Clin Invest, 2018, 128(5):2104-2115. DOI:10.1172/JCI96582. [24] Meng X, Huang Z, Teng F, et al. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy[J]. Cancer Treat Rev, 2015, 41(10):868-876. DOI:10.1016/j.ctrv. 2015.11.001. [25] Herter-Sprie GS, Koyama S, Korideck H, et al. Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer[J]. JCI Insight, 2016, 1(9):e87415. DOI:10.1172/jci. insight. 87415. [26] Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade[J]. Cancer Res, 2014, 74(19):5458-5468. DOI:10.1158/0008-5472. CAN-14-1258. [27] Gong X, Li X, Jiang T, et al. Combined radiotherapy and anti-pd-l1 antibody synergistically enhances antitumor effect in non-small cell lung cancer[J]. J Thorac Oncol, 2017, 12(7):1085-1097. DOI:10.1016/j.jtho. 2017.04.014. [28] Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect[J]. Cancer Immunol Res, 2015, 3(6):610-619. DOI:10.1158/2326-6066. CIR-14-0138. [29] Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice[J]. J Clin Invest, 2014, 124(2):687-695. DOI:10.1172/JCI67313. [30] Wang X, Schoenhals JE, Li A, et al. Suppression of type I IFN signaling in tumors mediates resistance to anti-PD-1 treatment that can be overcome by radiotherapy[J]. Cancer Res, 2017, 77(4):839-850. DOI:10.1158/0008-5472. CAN-15-3142. [31] Zhuang Y, Li S, Wang H, et al. PD-1 blockade enhances radio-immunotherapy efficacy in murine tumor models[J]. J Cancer Res Clin Oncol, 2018, 144(10):1909-1920. DOI:10.1007/s00432-018-2723-4. [32] Myers CJ, Lu B. Decreased survival after combining thoracic irradiation and an anti-PD-1 antibody correlated with increased T-cell infiltration into cardiac and lung tissues[J]. Int J Radiat Oncol Biol Phys, 2017, 99(5):1129-1136. DOI:10.1016/j.ijrobp. 2017.06.2452. [33] Marciscano AE, Ghasemzadeh A, Nirschl TR, et al. Elective nodal irradiation attenuates the combinatorial efficacy of stereotactic radiation therapy and immunotherapy[J]. Clin Cancer Res 2018. DOI:10.1158/1078-0432. CCR-17-3427. [34] Lee Y, Auh SL, Wang Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells:changing strategies for cancer treatment[J]. Blood, 2009, 114(3):589-595. DOI:10.1182/blood-2009-02-206870. [35] Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody[J]. Clin Cancer Res, 2009, 15(17):5379-5388. DOI:10.1158/1078-0432. CCR-09-0265. [36] Schaue D, Ratikan JA, Iwamoto KS, et al. Maximizing tumor immunity with fractionated radiation[J]. Int J Radiat Oncol Biol Phys, 2012, 83(4):1306-1310. DOI:10.1016/j.ijrobp. 2011.09.049. [37] Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010):a randomised controlled trial[J]. Lancet, 2016, 387(10027):1540-1550. DOI:10.1016/S0140-6736(15)01281-7. [38] 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. DOI:10.1016/S0140-6736(16)32517-X. [39] Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J]. N Engl J Med, 2016, 375(19):1823-1833. DOI:10.1056/NEJMoa1606774. [40] Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer:a secondary analysis of the KEYNOTE-001 phase 1 trial[J]. Lancet Oncol, 2017, 18(7):895-903. DOI:10.1016/S1470-2045(17)30380-7. [41] Haridass A. Developments in stereotactic body radiotherapy[J]. Cancers, 2018, 10(12):497. DOI:10.3390/cancers10120497. [42] Bernstein MB, Krishnan S, Hodge JW, et al. Immunotherapy and stereotactic ablative radiotherapy (ISABR):a curative approach?[J]. Nat Rev Clin Oncol, 2016, 13(8):516-524. DOI:10.1038/nrclinonc. 2016.30. [43] Theelen W, Peulen H, Lalezari F, et al. Randomized phase Ⅱ study of pembrolizumab after stereotactic radiotherapy (SBRT) versus pembrolizumab alone in patients with advanced non-small cell lung cancer:the PEMBRO-RT study[J]. J Clin Oncol, 2018, 36(15 suppl):9023. DOI:10.1200/JCO. 2018.36.15_suppl. 9023. [44] Foster CC, Sher DJ, Rusthoven CG, et al. Overall survival according to immunotherapy and radiation treatment for metastatic non-small-cell lung cancer:a National Cancer Database analysis[J]. Radiat oncol, 2019, 14(1):18. DOI:10.1186/s13014-019-1222-3. [45] Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects[J]. Nat Rev Clin Oncol, 2019, 16(2):123-135. DOI:10.1038/s41571-018-0119-7. [46] 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. DOI:10.1056/NEJMoa1809697. [47] National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology:non-small cell lung cancer (version 4.2018)[EB/OL].[2018-07-22]. https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf. [48] Naidoo J, Wang X, Woo KM, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy[J]. J Clin Oncol, 2017, 35(7):709-717. DOI:10.1200/JCO.2016.68.2005. [49] Boyer MJ, Gu L, Wang X, et al. Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer[J]. Lung Cancer, 2016, 98:76-78. DOI:10.1016/j.lungcan. 2016.05.014. [50] Zhao ZM, Liu SC, Xu XJ, et al. Treatment of skin reaction induced by nivolumab combined with radiotherapy in non-small cell lung cancer:a case report[J]. Chin Med Sci J, 2018, 33(3):183-187. DOI:10.24920/31805. [51] Fiorica F, Belluomini L, Stefanelli A, et al. Immune checkpoint inhibitor nivolumab and radiotherapy in pretreated lung cancer patients:efficacy and safety of combination[J]. Am J Clin Oncol, 2018,(published online Jan 31). DOI:10.1097/COC. 0000000000000428. [52] 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.
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