[an error occurred while processing this directive] | [an error occurred while processing this directive]
Research progress on the role of IDO signaling pathway in radiotherapy for non-small cell lung cancer
Wu Linfang1, Wang Chunyu1, Yang Yufan1, Bi Nan1, Wang Lyuhua1,2
1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; 2National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
Abstract Indoleamine 2,3-dioxygenase (IDO) is one of the rate-limiting enzymes that degrade tryptophan (Trp) into kynurenine (Kyn). Inflammatory factor IFN-γ mediates tumor′s immune escape by activating the IDO signaling pathway, upregulating theKyn/Trp (K/T ratio) and suppressing the activity of both CD+8T and regulatory T cells. Radiotherapy plays a major role in treating non-small cell lung cancer. It not only bi-directionally regulates immune response of the host, but also collaborates with immunosuppressive agents to kill tumors. Meanwhile, immune status of the host can affect the therapeutic effect of radiotherapy. In recent years, studies have shown that IDO activity levels change before and after radiotherapy and is related to clinical prognosis. Nevertheless, relevant mechanism remains unclear. This article aims to elucidate the application of IDO signaling pathway in radiotherapy for non-small cell lung cancer.
Corresponding Authors:
Wang Lyuhua;Email:wlhwq@yahoo.com
Cite this article:
Wu Linfang,Wang Chunyu,Yang Yufan et al. Research progress on the role of IDO signaling pathway in radiotherapy for non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(2): 219-222.
Wu Linfang,Wang Chunyu,Yang Yufan et al. Research progress on the role of IDO signaling pathway in radiotherapy for non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(2): 219-222.
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132. DOI:10.3322/caac.21338. [2] Liang J, Bi N, Wu S, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage Ⅲ non-small cell lung cancer:a multicenter randomized phase Ⅲ trial[J]. Ann Oncol, 2017, 28(4):777-783. DOI:10.1093/annonc/mdx009. [3] Senan S, Brade A, Wang LH, et al. PROCLAIM:Randomized phase Ⅲ trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer[J]. J Clin Oncol, 2016, 34(9):953-962. DOI:10.1200/JCO.2015.64.8824. [4] Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer[J]. N Engl J Med, 2017, 377(20):1919-1929. DOI:10.1056/NEJMoa1709937. [5] Godin-Ethier J, Hanafi LA, Piccirillo CA, et al. Indoleamine 2,3-dioxygenase expression in human cancers:clinical and immunologic perspectives[J]. Clin Cancer Res, 2011, 17(22):6985-6991. DOI:10.1158/1078-0432. CCR-11-1331. [6] Huang Jy, Larose TL, LuuHN, et al. Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)[J]. Int J Cancer, 2020, 146(9):2394-2405. DOI:10.1002/ijc.32555. [7] Jia Y, Wang H, Wang Y, et al. Low expression of Bin1, along with high expression of IDO in tumor tissue and draining lymph nodes, are predictors of poor prognosis for esophageal squamous cell cancer patients[J]. Int J Cancer, 2015, 137(5):1095-1106. DOI:10.1002/ijc.29481. [8] Spranger S, Spaapen RM, Zha Y, et al. Up-regulation of PD-L1, IDO, and T (regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells[J]. Sci Transl Med, 2013, 5(200):200ra116. DOI:10.1126/scitranslmed.3006504. [9] Hennequart M, Pilotte L, Cane S, et al. Constitutive IDO1 expression in human tumors is driven by cyclooxygenase-2 and mediates intrinsic immune resistance[J]. Cancer Immunol Res, 2017, 5(8):695-709. DOI:10.1158/2326-6066. CIR-16-0400. [10] Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase[J]. Nat Med, 2003, 9(10):1269-1274. DOI:10.1038/nm934. [11] Wainwright DA, Balyasnikova IV, Chang AL, et al. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival[J]. Clin Cancer Res, 2012, 18(22):6110-6121. DOI:10.1158/1078-0432. CCR-12-2130. [12] 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. [13] Pitroda SP, Chmura SJ, Weichselbaum RR. Integration of radiotherapy and immunotherapy for treatment of oligometastases[J]. Lancet Oncol, 2019, 20(8):e434-e442. DOI:10.1016/S1470-2045(19)30157-3. [14] Weichselbaum RR, Liang H, Deng L, et al. Radiotherapy and immunotherapy:a beneficial liaison?[J]. Nat Rev Clin Oncol, 2017, 14(6):365-379. DOI:10.1038/nrclinonc.2016.211. [15] Wu SY, Chen CL, Tseng PC, et al. Fractionated ionizing radiation facilitates interferon-γ signaling and anticancer activity in lung adenocarcinoma cells[J]. J Cell Physiol, 2019, DOI:10.1002/jcp.28258. [16] Qu S, Guo Y, Huang ST, et al. Inhibition of STAT1sensitizes radioresistant nasopharyngeal carcinoma cell line CNE-2R to radiotherapy[J]. Oncotarget, 2018, 9(9):8303-8310. DOI:10.18632/oncotarget.19690. [17] Zhu H, Wang Z, Xu Q, et al. Inhibition of STAT1sensitizes renal cell carcinoma cells to radiotherapy and chemotherapy[J]. Cancer Biol Ther, 2012, 13(6):401-407. DOI:10.4161/cbt.19291. [18] Frykns M, Dhar S, Oberg F, et al. STAT1signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines[J]. Int J Cancer, 2007, 120(1):189-195. DOI:10.1002/ijc.22291. [19] Soliman H, Mediavilla-Varela M, Antonia S. Indoleamine 2,3-dioxygenase:is it an immune suppressor?[J]. Cancer J, 2010, 16(4):354-359. DOI:10.1097/PPO.0b013e3181eb3343. [20] Monjazeb AM, Kent MS, Grossenbacher SK, et al. Blocking indolamine-2,3-dioxygenase rebound immune suppression boosts antitumor effects of radio-immunotherapy in murine models and spontaneous canine malignancies[J]. Clin Cancer Res, 2016, 22(17):4328-4340. DOI:10.1158/1078-0432. CCR-15-3026. [21] Wang W, Huang L, Jin JY, et al. IDO Immune status after chemoradiation may predict survival in lung cancer patients[J]. Cancer Res, 2018, 78(3):809-816. DOI:10.1158/0008-5472. CAN-17-2995. [22] Wang W, Huang L, Jin JY, et al. A validation study on IDO immune biomarkers for survival prediction in non-small cell lung cancer:radiation dose fractionation effect in early-stage disease[J]. Clin Cancer Res, 2020, 26(1):282-289. DOI:10.1158/1078-0432. CCR-19-1202. [23] Levy A, Nigro G, Sansonetti PJ, et al. Candidate immune biomarkers for radioimmunotherapy[J]. BiochimBiophys Acta Rev Cancer, 2017, 1868(1):58-68. DOI:10.1016/j.bbcan.2017.02.006. [24] Yu CP, Fu SF, Chen X, et al. The clinicopathological and prognostic significance of IDO1 expression in human solid tumors:evidence from a systematic review and meta-analysis[J]. Cell PhysiolBiochem, 2018, 49(1):134-143. DOI:10.1159/000492849. [25] Zhai L, Ladomersky E, Bell A, et al. Quantification of IDO1 enzyme activity in normal and malignant tissues[J]. Methods Enzymol, 2019, 629:235-256. DOI:10.1016/bs.mie.2019.07.006. [26] Prendergast GC, Mondal A, Dey S, et al. Inflammatory reprogramming with IDO1 inhibitors:turning immunologically unresponsive′Cold′ tumors′Hot′[J]. Trends Cancer, 2018, 4(1):38-58. DOI:10.1016/j.trecan.2017.11.005. [27] Friberg M, Jennings R, AlsarrajM, et al. Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection[J]. Int J Cancer, 2002, 101(2):151-155. DOI:10.1002/ijc.10645. [28] Liu X, Shin N, Koblish HK, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity[J]. Blood, 2010, 115(17):3520-3530. DOI:10.1182/blood-2009-09-246124. [29] Spranger S, Koblish HK, Horton B, et al. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment[J]. J Immunother Cancer, 2014, 2:3. DOI:10.1186/2051-1426-2-3. [30] Schalper KA, Carvajal-Hausdorf D, Mclaughlin J, et al. Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung cancer[J]. Clin Cancer Res, 2017, 23(2):370-378. DOI:10.1158/1078-0432. CCR-16-0150. [31] Volaric A, Gentzler R, Hall R,et al. Indoleamine-2,3-dioxygenase in non-small cell lung cancer:a targetable mechanism of immune resistance frequently coexpressed with PD-L1[J]. Am J Surg Pathol, 2018, 42(9):1216-1223. DOI:10.1097/PAS.0000000000001099. [32] Beatty GL,O′Dwyer PJ, Clark J, et al. First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies[J]. Clin Cancer Res, 2017, 23(13):3269-3276. DOI:10.1158/1078-0432. CCR-16-2272. [33] Yue EW, Sparks R, Polam P, et al. INCB24360(epacadostat), a highly potent and selective indoleamine-2,3-dioxygenase 1(IDO1) inhibitor for immuno-oncology[J]. ACS Med Chem Lett, 2017, 8(5):486-491. DOI:10.1021/acsmedchemlett.6b00391. [34] Gibney GT, Hamid O, Lutzky J, et al. Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma[J]. J Immunother Cancer, 2019, 7(1):80. DOI:10.1186/s40425-019-0562-8. [35] Mitchell TC, Hamid O, Smith DC, et al. Epacadostat plus pembrolizumab in patients with advanced solid tumors:phase I results from a multicenter, open-label phase Ⅰ/Ⅱ trial (ECHO-202/KEYNOTE-037)[J]. J Clin Oncol, 2018, 36(32):3223-3230. DOI:10.1200/JCO.2018.78.9602. [36] Muller AJ, Duhadaway JB, Donover PS, et al. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy[J]. Nat Med, 2005, 11(3):312-319. DOI:10.1038/nm1196. [37] Soliman HH, Minton SE, Han HS,et al. A phase I study of indoximod in patients with advanced malignancies[J]. Oncotarget, 2016, 7(16):22928-22938. DOI:10.18632/oncotarget.8216. [38] 张康平,张琪,于恺英,等. 吲哚胺2,3-双加氧酶抑制剂临床研究现状[J]. 中国医学前沿杂志(电子版), 2020,12(1):20-26. DOI:10.12037/YXQY.2020.01-04. Zhang KP, Zhang Q, Yu KY, et al. Current clinical research of indoleamine 2, 3-dioxygenase inhibitors[J]. Chin J Front Med Sci (Elec Ver), 2020,12(1):20-26. DOI:10.12037/YXQY.2020.01-04. [39] LiuM, LiZ, YaoW, et al. IDO inhibitor synergized with radiotherapy to delay tumor growth by reversing T cell exhaustion[J]. Mol Med Rep, 2020, 21(1):445-453. DOI:10.3892/mmr.2019.10816. [40] LadomerskyE, ZhaiL, LenzenA, et al. IDO1 inhibition synergizes with radiation and PD-1 blockade to durably increase survival against advanced glioblastoma[J]. Clin Cancer Res, 2018, 24(11):2559-2573. DOI:10.1158/1078-0432. CCR-17-3573. [41] Johnson TS, Aguilera D, Al-basheer A, et al. PDCT-06. Radio-immunotherapy using the ido-inhibitor indoximod in combination with re-irradiation for children with progressive brain tumors in the phase 1setting:an updated report of safety and tolerability (NCT02502708)[J]. Neuro-Oncology, 2017,19(Suppl6):vi185-vi185. [42] Li M, Bolduc AR, Hoda MN, et al. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma[J]. J Immunother Cancer, 2014, 2:21. DOI:10.1186/2051-1426-2-21. [43] Smith C, Chang MY, Parker KH, et al. IDO is a nodal pathogenic driver of lung cancer and metastasis development[J]. Cancer Discov, 2012, 2(8):722-735. DOI:10.1158/2159-8290. CD-12-0014. [44] Muller AJ, Manfredi MG, Zakharia Y, et al. Inhibiting IDO pathways to treat cancer:lessons from the ECHO-301 trial and beyond[J]. SeminImmunopathol, 2019, 41(1):41-48. DOI:10.1007/s00281-018-0702-0.
2022, Vol. 31 
