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Research advances in immune response of stereotactic body radiotherapy
Liu Xiaojun1,2,3, Ma Wen1,2, Ma Chenru1,2, Qiao Wanjia3, Li Shuping1,2
1The Second Division of Radiation Oncology, Gansu Provincial Hospital, Lanzhou 730000, China; 2The First Clinical Medical College, Chinese Medical University of Gansu, Lanzhou 730000, China; 3The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
Abstract The mechanisms of radiotherapy (RT) in cancer treatment are both by immunity and non-immunity pathways. According to different absorbed doses, the immune modulating effect of RT comprises of tumor microenvironment modulating effect, immune-modulatory effect as well as immune-ablative effect. RT could improve the therapeutic efficacy of immunotherapy, while immunotherapy could enlarge the immunity activating effect induced by RT in turn. Therefore, RT is emerging as a valuable partner of cancer immunotherapy. RT regimens have a vital impact on immunity within tumor microenvironment. Stereotactic body RT (SBRT) has obvious advantages regarding interferon production and abscopal effect. At present, potentially sub-ablative RT regimen of 8 Gy plus 3 fractionations is the most widely used SBRT. Several novel RT regimens, such as hybrid fractionation, singular site irradiation and multisite irradiation, have been designed to maximize the immune induction effect and improve the combination efficacy with immunotherapy in metastatic malignancies. In this review, the latest advances in the immune effect of RT were discussed and novel SBRT regimens were proposed, aiming to provide reference for enhancing the efficacy of radio-immunotherapy or immuno-radiotherapy in clinical practice.
Fund:; Fund program: Natural Science Foundation of Gansu Province (21JR7RA618)
Corresponding Authors:
Li Shuping, Email: shupingli2020@163.com
Cite this article:
Liu Xiaojun,Ma Wen,Ma Chenru et al. Research advances in immune response of stereotactic body radiotherapy[J]. Chinese Journal of Radiation Oncology, 2023, 32(2): 159-163.
Liu Xiaojun,Ma Wen,Ma Chenru et al. Research advances in immune response of stereotactic body radiotherapy[J]. Chinese Journal of Radiation Oncology, 2023, 32(2): 159-163.
[1] 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. [2] Shibamoto Y, Miyakawa A, Otsuka S, et al. Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?[J]. J Radiat Res, 2016,57Suppl 1(Suppl 1):i76-i82. DOI: 10.1093/jrr/rrw015. [3] Tang J, Malachowska B, Wu X, et al.Repurposing radiation therapy for immuno-oncology[J]. Clin Oncol (R Coll Radiol), 2021,33(11):683-693. DOI: 10.1016/j.clon.2021. 08.015. [4] Schadt L, Sparano C, Schweiger NA, et al. Cancer- cell-intrinsic cGAS expression mediates tumor immunogenicity[J]. Cell Rep, 2019,29(5):1236-1248.e7. DOI: 10.1016/j.celrep.2019.09.065. [5] Harding SM, Benci JL, Irianto J, et al.Mitotic progression following DNA damage enables pattern recognition within micronuclei[J]. Nature, 2017,548(7668):466-470. DOI: 10.1038/nature23470. [6] 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. [7] Habets TH, Oth T, Houben AW, et al.Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response[J]. PLoS One, 2016,11(7):e0159515. DOI: 10.1371/journal.pone.0159515. [8] Zhou P, Chen D, Zhu B, et al.Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma[J]. Front Immunol, 2020,11:594212. DOI: 10.3389/fimmu.2020. 594212. [9] Barsoumian HB, Ramapriyan R, Younes AI, et al.Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma[J]. J Immunother Cancer, 2020,8(2): e000537. DOI: 10.1136/jitc-2020-000537. [10] Clark PA, Sriramaneni RN, Bates AM, et al.Low-dose radiation potentiates the propagation of anti-tumor immunity against melanoma tumor in the brain after in situ vaccination at a tumor outside the brain[J]. Radiat Res, 2021,195(6):522-540. DOI: 10.1667/RADE-20- 00237.1. [11] Folkert MR, Timmerman RD.Stereotactic ablative body radiosurgery (SABR) or stereotactic body radiation therapy (SBRT)[J]. Adv Drug Deliv Rev, 2017,109:3-14. DOI: 10.1016/j.addr.2016.11.005. [12] Lin AJ, Roach M, Bradley J, et al.Combining stereotactic body radiation therapy with immunotherapy: current data and future directions[J]. Transl Lung Cancer Res, 2019,8(1):107-115. DOI: 10.21037/tlcr.2018.08.16. [13] Muraro E, Furlan C, Avanzo M, et al.Local high-dose radiotherapy induces systemic immunomodulating effects of potential therapeutic relevance in oligometastatic breast cancer[J]. Front Immunol, 2017,8:1476. DOI: 10.3389/fimmu.2017.01476. [14] 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. [15] Liu H, Sintay B, Pearman K, et al. A hybrid planning strategy for stereotactic body radiation therapy of early stage non-small-cell lung cancer[J]. J Appl Clin Med Phys, 2018,19(6):117-123. DOI:10.1002/acm2.12450. [16] Savage T, Pandey S, Guha C.Postablation modulation after single high-dose radiation therapy improves tumor control via enhanced immunomodulation[J]. Clin Cancer Res, 2020,26(4):910-921. DOI: 10.1158/1078-0432.CCR-18-3518. [17] Peulen H, Franssen G, Belderbos J, et al.SBRT combined with concurrent chemoradiation in stage III NSCLC: feasibility study of the phase I hybrid trial[J]. Radiother Oncol, 2020,142:224-229. DOI: 10.1016/j.radonc.2019. 07.015. [18] Theelen W, Peulen H, Lalezari F, et al.Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: results of the PEMBRO-RT phase 2 randomized clinical trial[J]. JAMA Oncol, 2019,5(9):1276-1282. DOI: 10.1001/jamaoncol. 2019.1478. [19] Bauml JM, Mick R, Ciunci C, et al.Pembrolizumab after completion of locally ablative therapy for oligometastatic non-small cell lung cancer: a phase 2 trial[J]. JAMA Oncol, 2019,5(9):1283-1290. DOI: 10.1001/jamaoncol.2019. 1449. [20] Luke JJ, Lemons JM, Karrison TG, et al.Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors[J]. J Clin Oncol, 2018,36(16):1611-1618. DOI: 10.1200/JCO.2017.76.2229. [21] Arina A, Beckett M, Fernandez C, et al.Tumor- reprogrammed resident T cells resist radiation to control tumors[J]. Nat Commun, 2019,10(1):3959. DOI: 10.1038/s41467-019-11906-2. [22] Menon H, Chen D, Ramapriyan R, et al.Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy[J]. J Immunother Cancer, 2019,7(1):237. DOI: 10.1186/s40425-019-0718-6. [23] Faivre-Finn C, Vicente D, Kurata T, et al.Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC-an update from the PACIFIC trial[J]. J Thorac Oncol, 2021,16(5):860-867. DOI: 10.1016/j.jtho.2020. 12.015. [24] Demaria S, Guha C, Schoenfeld J, et al.Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?[J]. J Immunother Cancer, 2021,9(4) :e002038. DOI: 10.1136/jitc-2020- 002038. [25] Morris ZS, Guy EI, Francis DM, et al.In situ tumor vaccination by combining local radiation and tumor-specific antibody or immunocytokine treatments[J]. Cancer Res, 2016,76(13):3929-3941. DOI: 10.1158/0008-5472.CAN-15-2644. [26] 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. [27] Jagodinsky JC, Morris ZS.Priming and propagating anti-tumor immunity: focal hypofractionated radiation for in situ vaccination and systemic targeted radionuclide theranostics for immunomodulation of tumor microenvironments[J]. Semin Radiat Oncol, 2020,30(2):181-186. DOI: 10.1016/j.semradonc.2019.12.008. [28] Wei SC, Levine JH, Cogdill AP, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade[J]. Cell, 2017,170(6):1120-1133.e17. DOI: 10.1016/j.cell.2017.07.024. [29] Verma V, Shrimali RK, Ahmad S, et al.PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1+CD38hi cells and anti-PD-1 resistance[J]. Nat Immunol, 2019,20(9):1231-1243. DOI: 10.1038/s41590-019-0441-y. [30] Derer A, Spiljar M, Bäumler M, et al.Chemoradiation increases PD-L1 expression in certain melanoma and glioblastoma cells[J]. Front Immunol, 2016,7:610. DOI: 10.3389/fimmu.2016.00610. [31] 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. [32] Kiess AP, Wolchok JD, Barker CA, et al.Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment[J]. Int J Radiat Oncol Biol Phys, 2015,92(2):368-375. DOI: 10.1016/j.ijrobp.2015.01.004. [33] Galon J, Bruni D.Approaches to treat immune hot, altered and cold tumours with combination immunotherapies[J]. Nat Rev Drug Discov, 2019,18(3):197-218. DOI: 10.1038/s41573-018-0007-y.
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