{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:22:07Z","timestamp":1791897727533,"version":"4.3.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Radiotherapy (XRT), a well-known activator of the inflammasome and immune priming, is in part capable of reversing resistance to anti-PD1 treatment. The NLRP3 inflammasome is a pattern recognition receptor which is activated by both exogenous and endogenous stimuli, leading to a downstream inflammatory response. Although NLRP3 is typically recognized for its role in exacerbating XRT-induced tissue damage, the NLRP3 inflammasome can also yield an effective antitumor response when used in proper dosing and sequencing with XRT. However, whether NLRP3 agonist boosts radiation-induced immune priming and promote abscopal responses in anti-PD1 resistant model is still unknown. Therefore, in this study, we paired intratumoral injection of an NLRP3 agonist with XRT to stimulate the immune system in both wild type (344SQ-P) and anti-PD1 resistant (344SQ-R) murine-implanted lung adenocarcinoma models. We found that the combination of XRT\u2009+\u2009NLPR3 agonist enhanced the control of implanted lung adenocarcinoma primary as well as secondary tumors in a radiological dose-dependent manner, in which 12Gyx3 fractions of stereotactic XRT was better than 5Gyx3, while 1Gyx2 did not improve the NLRP3 effect. Survival and tumor growth data also showed significant abscopal response with the triple therapy (12Gyx3\u2009+\u2009NLRP3 agonist\u2009+\u2009\u03b1-PD1) in both 344SQ-P and 344SQ-R aggressively growing models. Multiple pro-inflammatory cytokines (IL-1b, IL-4, IL-12, IL-17, IFN-\u03b3 and GM-CSF) were elevated in the serum of mice treated with XRT\u2009+\u2009NLRP3 or triple therapy. The Nanostring results showed that NLRP3 agonist is capable of increasing antigen presentation, innate function, and T-cell priming. This study can be of particular importance to treat patients with immunologically-cold solid tumors whom are also refractory to prior checkpoint treatments.<\/jats:p>","DOI":"10.1007\/s00262-023-03471-x","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T06:01:58Z","timestamp":1686204118000},"page":"3003-3012","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["NLRP3 agonist enhances radiation-induced immune priming and promotes abscopal responses in anti-PD1 resistant model"],"prefix":"10.1007","volume":"72","author":[{"given":"Hampartsoum B.","family":"Barsoumian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Bertolet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Sezen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Riad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angelica","family":"Cortez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"3471_CR1","doi-asserted-by":"publisher","first-page":"7204","DOI":"10.18632\/oncotarget.23208","volume":"9","author":"L Chen","year":"2018","unstructured":"Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L (2018) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9:7204\u20137218. https:\/\/doi.org\/10.18632\/oncotarget.23208","journal-title":"Oncotarget"},{"key":"3471_CR2","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3390\/ijms22020872","volume":"22","author":"M Sharma","year":"2021","unstructured":"Sharma M, de Alba E (2021) Structure, activation and regulation of NLRP3 and AIM2 inflammasomes. Int J Mol Sci 22:872. https:\/\/doi.org\/10.3390\/ijms22020872","journal-title":"Int J Mol Sci"},{"key":"3471_CR3","doi-asserted-by":"publisher","first-page":"e27","DOI":"10.4110\/in.2018.18.e27","volume":"18","author":"JS Roh","year":"2018","unstructured":"Roh JS, Sohn DH (2018) Damage-associated molecular patterns in inflammatory diseases. Immune Netw 18:e27. https:\/\/doi.org\/10.4110\/in.2018.18.e27","journal-title":"Immune Netw"},{"key":"3471_CR4","doi-asserted-by":"publisher","first-page":"4399","DOI":"10.3892\/mmr.2018.9427","volume":"18","author":"D Li","year":"2018","unstructured":"Li D, Ren W, Jiang Z, Zhu L (2018) Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Mol Med Rep 18:4399\u20134409. https:\/\/doi.org\/10.3892\/mmr.2018.9427","journal-title":"Mol Med Rep"},{"key":"3471_CR5","doi-asserted-by":"publisher","first-page":"106761","DOI":"10.1016\/j.intimp.2020.106761","volume":"86","author":"M Ashrafizadeh","year":"2020","unstructured":"Ashrafizadeh M, Farhood B, Eleojo Musa A, Taeb S, Najafi M (2020) Damage-associated molecular patterns in tumor radiotherapy. Int Immunopharmacol 86:106761. https:\/\/doi.org\/10.1016\/j.intimp.2020.106761","journal-title":"Int Immunopharmacol"},{"key":"3471_CR6","doi-asserted-by":"publisher","first-page":"17414","DOI":"10.1073\/pnas.1108945108","volume":"108","author":"W Kratky","year":"2011","unstructured":"Kratky W, Reis e Sousa C, Oxenius A, Sporri R (2011) Direct activation of antigen-presenting cells is required for CD8+ T-cell priming and tumor vaccination. Proc Natl Acad Sci U S A 108:17414\u201317419. https:\/\/doi.org\/10.1073\/pnas.1108945108","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3471_CR7","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","volume":"41","author":"L Deng","year":"2014","unstructured":"Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, Huang X, Gajewski TF, Chen ZJ, Fu YX, Weichselbaum RR (2014) STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41:843\u2013852. https:\/\/doi.org\/10.1016\/j.immuni.2014.10.019","journal-title":"Immunity"},{"key":"3471_CR8","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1158\/0008-5472.CAN-10-2820","volume":"71","author":"BC Burnette","year":"2011","unstructured":"Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, Fu YX, Auh SL (2011) The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res 71:2488\u20132496. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-2820","journal-title":"Cancer Res"},{"key":"3471_CR9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13045-018-0647-8","volume":"11","author":"Y Liu","year":"2018","unstructured":"Liu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J (2018) Abscopal effect of radiotherapy combined with immune checkpoint inhibitors. J Hematol Oncol 11:104. https:\/\/doi.org\/10.1186\/s13045-018-0647-8","journal-title":"J Hematol Oncol"},{"key":"3471_CR10","doi-asserted-by":"publisher","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","volume":"15","author":"MZ Dewan","year":"2009","unstructured":"Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 15:5379\u20135388. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-0265","journal-title":"Clin Cancer Res"},{"key":"3471_CR11","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.ijrobp.2021.06.041","volume":"111","author":"Y Hu","year":"2021","unstructured":"Hu Y, Paris S, Barsoumian H, Abana CO, He K, Wasley M, Younes AI, Masrorpour F, Chen D, Yang L, Dunn JD, Zhang J, Gandhi S, Nguyen QN, Cortez MA, Welsh J (2021) Radiation therapy enhanced by NBTXR3 nanoparticles overcomes anti-PD1 resistance and evokes abscopal effects. Int J Radiat Oncol Biol Phys 111:647\u2013657. https:\/\/doi.org\/10.1016\/j.ijrobp.2021.06.041","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3471_CR12","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1158\/0008-5472.CAN-15-3142","volume":"77","author":"X Wang","year":"2017","unstructured":"Wang X, Schoenhals JE, Li A, Valdecanas DR, Ye H, Zang F, Tang C, Tang M, Liu CG, Liu X, Krishnan S, Allison JP, Sharma P, Hwu P, Komaki R, Overwijk WW, Gomez DR, Chang JY, Hahn SM, Cortez MA, Welsh JW (2017) Suppression of type I IFN signaling in tumors mediates resistance to anti-PD-1 treatment that can be overcome by radiotherapy. Cancer Res 77:839\u2013850. https:\/\/doi.org\/10.1158\/0008-5472.CAN-15-3142","journal-title":"Cancer Res"},{"key":"3471_CR13","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1158\/2326-6066.Cir-19-0744","volume":"8","author":"D Chen","year":"2020","unstructured":"Chen D, Barsoumian HB, Yang L, Younes AI, Verma V, Hu Y, Menon H, Wasley M, Masropour F, Mosaffa S, Ozgen T, Klein K, Cortez MA, Welsh JW (2020) SHP-2 and PD-L1 inhibition combined with radiotherapy enhances systemic antitumor effects in an anti-PD-1-resistant model of non-small cell lung cancer. Cancer Immunol Res 8:883\u2013894. https:\/\/doi.org\/10.1158\/2326-6066.Cir-19-0744","journal-title":"Cancer Immunol Res"},{"key":"3471_CR14","doi-asserted-by":"publisher","first-page":"4840","DOI":"10.1038\/s41467-020-18617-z","volume":"11","author":"MA Cortez","year":"2020","unstructured":"Cortez MA, Masrorpour F, Ivan C, Zhang J, Younes AI, Lu Y, Estecio MR, Barsoumian HB, Menon H, Caetano MDS, Ramapriyan R, Schoenhals JE, Wang X, Skoulidis F, Wasley MD, Calin G, Hwu P, Welsh JW (2020) Bone morphogenetic protein 7 promotes resistance to immunotherapy. Nat Commun 11:4840. https:\/\/doi.org\/10.1038\/s41467-020-18617-z","journal-title":"Nat Commun"},{"key":"3471_CR15","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-22-0547","author":"K He","year":"2023","unstructured":"He K, Barsoumian HB, Puebla-Osorio N, Hu Y, Sezen D, Wasley MD, Bertolet G, Zhang J, Leuschner C, Yang L, Kettlun Leyton CS, Fowlkes NW, Green MM, Hettrick L, Chen D, Masropour F, Gu M, Maazi H, Revenko AS, Cortez MA, Welsh JW (2023) Inhibition of STAT6 with antisense oligonucleotides enhances the systemic antitumor effects of radiotherapy and anti-PD1 in metastatic non-small cell lung cancer. Cancer Immunol Res. https:\/\/doi.org\/10.1158\/2326-6066.CIR-22-0547","journal-title":"Cancer Immunol Res"},{"key":"3471_CR16","doi-asserted-by":"publisher","first-page":"639815","DOI":"10.3389\/fcell.2021.639815","volume":"9","author":"JC Escolano","year":"2021","unstructured":"Escolano JC, Taubenberger AV, Abuhattum S, Schweitzer C, Farrukh A, Del Campo A, Bryant CE, Guck J (2021) Compliant substrates enhance macrophage cytokine release and NLRP3 inflammasome formation during their pro-inflammatory response. Front Cell Dev Biol 9:639815. https:\/\/doi.org\/10.3389\/fcell.2021.639815","journal-title":"Front Cell Dev Biol"},{"key":"3471_CR17","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1172\/JCI133055","volume":"130","author":"B Theivanthiran","year":"2020","unstructured":"Theivanthiran B, Evans KS, DeVito NC, Plebanek M, Sturdivant M, Wachsmuth LP, Salama AK, Kang Y, Hsu D, Balko JM, Johnson DB, Starr M, Nixon AB, Holtzhausen A, Hanks BA (2020) A tumor-intrinsic PD-L1\/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy. J Clin Investig 130:2570\u20132586. https:\/\/doi.org\/10.1172\/JCI133055","journal-title":"J Clin Investig"},{"key":"3471_CR18","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3389\/fcell.2020.00140","volume":"8","author":"S Huang","year":"2020","unstructured":"Huang S, Che J, Chu Q, Zhang P (2020) The role of NLRP3 inflammasome in radiation-induced cardiovascular injury. Front Cell Dev Biol 8:140. https:\/\/doi.org\/10.3389\/fcell.2020.00140","journal-title":"Front Cell Dev Biol"},{"key":"3471_CR19","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","volume":"6","author":"K Shah","year":"2021","unstructured":"Shah K, Al-Haidari A, Sun J, Kazi JU (2021) T Cell Receptor (TCR) signaling in health and disease. Signal Transduct Target Ther 6:412. https:\/\/doi.org\/10.1038\/s41392-021-00823-w","journal-title":"Signal Transduct Target Ther"},{"key":"3471_CR20","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646\u2013674. https:\/\/doi.org\/10.1016\/j.cell.2011.02.013","journal-title":"Cell"},{"key":"3471_CR21","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/s0140-6736(00)04046-0","volume":"357","author":"F Balkwill","year":"2001","unstructured":"Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539\u2013545. https:\/\/doi.org\/10.1016\/s0140-6736(00)04046-0","journal-title":"Lancet"},{"key":"3471_CR22","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s10555-010-9227-2","volume":"29","author":"G Solinas","year":"2010","unstructured":"Solinas G, Marchesi F, Garlanda C, Mantovani A, Allavena P (2010) Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev 29:243\u2013248. https:\/\/doi.org\/10.1007\/s10555-010-9227-2","journal-title":"Cancer Metastasis Rev"},{"key":"3471_CR23","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.3389\/fimmu.2020.01444","volume":"11","author":"S Hamarsheh","year":"2020","unstructured":"Hamarsheh S, Zeiser R (2020) NLRP3 inflammasome activation in cancer: a double-edged sword. Front Immunol 11:1444. https:\/\/doi.org\/10.3389\/fimmu.2020.01444","journal-title":"Front Immunol"},{"key":"3471_CR24","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa345","author":"M Ju","year":"2020","unstructured":"Ju M, Bi J, Wei Q, Jiang L, Guan Q, Zhang M, Song X, Chen T, Fan J, Li X, Wei M, Zhao L (2020) Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer. Brief Bioinform. https:\/\/doi.org\/10.1093\/bib\/bbaa345","journal-title":"Brief Bioinform"},{"key":"3471_CR25","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1084\/jem.20100050","volume":"207","author":"IC Allen","year":"2010","unstructured":"Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207:1045\u20131056. https:\/\/doi.org\/10.1084\/jem.20100050","journal-title":"J Exp Med"},{"key":"3471_CR26","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.immuni.2015.08.013","volume":"43","author":"J Dupaul-Chicoine","year":"2015","unstructured":"Dupaul-Chicoine J, Arabzadeh A, Dagenais M, Douglas T, Champagne C, Morizot A, Rodrigue-Gervais IG, Breton V, Colpitts SL, Beauchemin N, Saleh M (2015) The Nlrp3 inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell tumoricidal activity. Immunity 43:751\u2013763. https:\/\/doi.org\/10.1016\/j.immuni.2015.08.013","journal-title":"Immunity"},{"key":"3471_CR27","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.immuni.2010.03.003","volume":"32","author":"MH Zaki","year":"2010","unstructured":"Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD (2010) The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32:379\u2013391. https:\/\/doi.org\/10.1016\/j.immuni.2010.03.003","journal-title":"Immunity"},{"key":"3471_CR28","doi-asserted-by":"publisher","first-page":"4912","DOI":"10.4049\/jimmunol.1002046","volume":"185","author":"MH Zaki","year":"2010","unstructured":"Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti TD (2010) IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. J Immunol 185:4912\u20134920. https:\/\/doi.org\/10.4049\/jimmunol.1002046","journal-title":"J Immunol"},{"key":"3471_CR29","doi-asserted-by":"publisher","first-page":"26280","DOI":"10.1038\/srep26280","volume":"6","author":"E Salaro","year":"2016","unstructured":"Salaro E, Rambaldi A, Falzoni S, Amoroso FS, Franceschini A, Sarti AC, Bonora M, Cavazzini F, Rigolin GM, Ciccone M, Audrito V, Deaglio S, Pelegrin P, Pinton P, Cuneo A, Di Virgilio F (2016) Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death. Sci Rep 6:26280. https:\/\/doi.org\/10.1038\/srep26280","journal-title":"Sci Rep"},{"key":"3471_CR30","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/labinvest.2013.126","volume":"94","author":"Q Wei","year":"2014","unstructured":"Wei Q, Mu K, Li T, Zhang Y, Yang Z, Jia X, Zhao W, Huai W, Guo P, Han L (2014) Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression. Lab Investig 94:52\u201362. https:\/\/doi.org\/10.1038\/labinvest.2013.126","journal-title":"Lab Investig"},{"key":"3471_CR31","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/labinvest.2015.63","volume":"95","author":"Q Wei","year":"2015","unstructured":"Wei Q, Guo P, Mu K, Zhang Y, Zhao W, Huai W, Qiu Y, Li T, Ma X, Liu Y, Chen X, Han L (2015) Estrogen suppresses hepatocellular carcinoma cells through ER\u03b2-mediated upregulation of the NLRP3 inflammasome. Lab Investig 95:804\u2013816. https:\/\/doi.org\/10.1038\/labinvest.2015.63","journal-title":"Lab Investig"},{"key":"3471_CR32","doi-asserted-by":"publisher","first-page":"7576","DOI":"10.1158\/1078-0432.Ccr-19-0795","volume":"25","author":"MS Caetano","year":"2019","unstructured":"Caetano MS, Younes AI, Barsoumian HB, Quigley M, Menon H, Gao C, Spires T, Reilly TP, Cadena AP, Cushman TR, Schoenhals JE, Li A, Nguyen QN, Cortez MA, Welsh JW (2019) Triple therapy with MerTK and PD1 inhibition plus radiotherapy promotes abscopal antitumor immune responses. Clin Cancer Res 25:7576\u20137584. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-19-0795","journal-title":"Clin Cancer Res"},{"key":"3471_CR33","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/s2213-2600(20)30391-x","volume":"9","author":"W Theelen","year":"2021","unstructured":"Theelen W, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts J, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW (2021) Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med 9:467\u2013475. https:\/\/doi.org\/10.1016\/s2213-2600(20)30391-x","journal-title":"Lancet Respir Med"},{"key":"3471_CR34","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1158\/2326-6066.Cir-18-0793","volume":"7","author":"JW Welsh","year":"2019","unstructured":"Welsh JW, Tang C, de Groot P, Naing A, Hess KR, Heymach JV, Papadimitrakopoulou VA, Cushman TR, Subbiah V, Chang JY, Simon GR, Ramapriyan R, Barsoumian HB, Menon H, Cortez MA, Massarelli E, Nguyen Q, Sharma P, Allison JP, Diab A, Verma V, Raju U, Shaaban SG, Dadu R, Cabanillas ME, Wang K, Anderson C, Gomez DR, Hahn S, Komaki R, Hong DS (2019) Phase II trial of ipilimumab with stereotactic radiation therapy for metastatic disease: outcomes, toxicities, and low-dose radiation-related abscopal responses. Cancer Immunol Res 7:1903\u20131909. https:\/\/doi.org\/10.1158\/2326-6066.Cir-18-0793","journal-title":"Cancer Immunol Res"},{"key":"3471_CR35","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.ijrobp.2003.09.012","volume":"58","author":"S Demaria","year":"2004","unstructured":"Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, Formenti SC (2004) Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 58:862\u2013870. https:\/\/doi.org\/10.1016\/j.ijrobp.2003.09.012","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3471_CR36","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.4049\/jimmunol.1303051","volume":"194","author":"VM Stoecklein","year":"2015","unstructured":"Stoecklein VM, Osuka A, Ishikawa S, Lederer MR, Wanke-Jellinek L, Lederer JA (2015) Radiation exposure induces inflammasome pathway activation in immune cells. J Immunol 194:1178\u20131189. https:\/\/doi.org\/10.4049\/jimmunol.1303051","journal-title":"J Immunol"},{"key":"3471_CR37","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.4049\/jimmunol.2000217","volume":"205","author":"H Ito","year":"2020","unstructured":"Ito H, Kimura H, Karasawa T, Hisata S, Sadatomo A, Inoue Y, Yamada N, Aizawa E, Hishida E, Kamata R, Komada T, Watanabe S, Kasahara T, Suzuki T, Horie H, Kitayama J, Sata N, Yamaji-Kegan K, Takahashi M (2020) NLRP3 inflammasome activation in lung vascular endothelial cells contributes to intestinal ischemia\/reperfusion-induced acute lung injury. J Immunol 205:1393\u20131405. https:\/\/doi.org\/10.4049\/jimmunol.2000217","journal-title":"J Immunol"},{"key":"3471_CR38","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.ijrobp.2020.02.643","volume":"107","author":"X Li","year":"2020","unstructured":"Li X, Gong Y, Li D, Xiang L, Ou Y, Jiang L, Shu P, Liu X, Guo F, Qin D, Mo Z, Qin Q, Wang X, Wang Y (2020) Low-dose radiation therapy promotes radiation pneumonitis by activating NLRP3 inflammasome. Int J Radiat Oncol Biol Phys 107:804\u2013814. https:\/\/doi.org\/10.1016\/j.ijrobp.2020.02.643","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3471_CR39","doi-asserted-by":"publisher","first-page":"e2579","DOI":"10.1038\/cddis.2016.460","volume":"8","author":"YG Liu","year":"2017","unstructured":"Liu YG, Chen JK, Zhang ZT, Ma XJ, Chen YC, Du XM, Liu H, Zong Y, Lu GC (2017) NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages. Cell Death Dis 8:e2579. https:\/\/doi.org\/10.1038\/cddis.2016.460","journal-title":"Cell Death Dis"},{"key":"3471_CR40","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.etap.2015.02.019","volume":"39","author":"SH Sohn","year":"2015","unstructured":"Sohn SH, Lee JM, Park S, Yoo H, Kang JW, Shin D, Jung KH, Lee YS, Cho J, Bae H (2015) The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice. Environ Toxicol Pharmacol 39:917\u2013926. https:\/\/doi.org\/10.1016\/j.etap.2015.02.019","journal-title":"Environ Toxicol Pharmacol"},{"key":"3471_CR41","doi-asserted-by":"publisher","first-page":"115495","DOI":"10.1016\/j.taap.2021.115495","volume":"418","author":"T Wu","year":"2021","unstructured":"Wu T, Gao J, Liu W, Cui J, Yang M, Guo W, Wang FY (2021) NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling. Toxicol Appl Pharmacol 418:115495. https:\/\/doi.org\/10.1016\/j.taap.2021.115495","journal-title":"Toxicol Appl Pharmacol"},{"key":"3471_CR42","doi-asserted-by":"publisher","first-page":"eabc6998","DOI":"10.1126\/sciimmunol.abc6998","volume":"6","author":"C Han","year":"2021","unstructured":"Han C, Godfrey V, Liu Z, Han Y, Liu L, Peng H, Weichselbaum RR, Zaki H, Fu YX (2021) The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation. Sci Immunol 6:eabc6998. https:\/\/doi.org\/10.1126\/sciimmunol.abc6998","journal-title":"Sci Immunol"},{"key":"3471_CR43","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1038\/nm.2028","volume":"15","author":"F Ghiringhelli","year":"2009","unstructured":"Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, G\u00e9nin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, Andr\u00e9 F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15:1170\u20131178. https:\/\/doi.org\/10.1038\/nm.2028","journal-title":"Nat Med"},{"key":"3471_CR44","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3389\/fphar.2015.00262","volume":"6","author":"BZ Shao","year":"2015","unstructured":"Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C (2015) NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol 6:262. https:\/\/doi.org\/10.3389\/fphar.2015.00262","journal-title":"Front Pharmacol"},{"key":"3471_CR45","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/ni.1703","volume":"10","author":"L Franchi","year":"2009","unstructured":"Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G (2009) The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 10:241\u2013247. https:\/\/doi.org\/10.1038\/ni.1703","journal-title":"Nat Immunol"},{"key":"3471_CR46","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/s1097-2765(02)00599-3","volume":"10","author":"F Martinon","year":"2002","unstructured":"Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417\u2013426. https:\/\/doi.org\/10.1016\/s1097-2765(02)00599-3","journal-title":"Mol Cell"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-023-03471-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-023-03471-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-023-03471-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T23:25:51Z","timestamp":1691623551000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-023-03471-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["3471"],"URL":"https:\/\/doi.org\/10.1007\/s00262-023-03471-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2570782\/v1","asserted-by":"object"}]},"ISSN":["0340-7004","1432-0851"],"issn-type":[{"value":"0340-7004","type":"print"},{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,8]]},"assertion":[{"value":"10 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"JWW reports research support from GlaxoSmithKline, Bristol Meyers Squibb, Merck, Nanobiotix, RefleXion, Alkermes, Artidis, Mavu Pharma, Takeda, Varian, Checkmate Pharmaceuticals, HotSpot Therapeutics, Inc., Gilead and Kiromic. JWW serves\/served on the scientific advisory board for Legion Healthcare Partners, RefleXion Medical, MolecularMatch, Merck, AstraZeneca, Aileron Therapeutics, OncoResponse, Checkmate Pharmaceuticals, Mavu Pharma, Alpine Immune Sciences, Ventana Medical Systems, Nanobiotix, China Medical Tribune, GI Innovation, Genentech and Nanorobotix. JWW serves as consultant for Lifescience Dynamics Limited. JWW has\/had Speaking Engagements for Ventana Medical Systems, US Oncology, Alkermes, Boehringer Ingelheim, Accuray and RSS. JWW holds\/held stock or ownership in Alpine Immune Sciences, Checkmate Pharmaceuticals, Healios, Mavu Pharma, Legion Healthcare Partners, MolecularMatch, Nanorobotix, OncoResponse, and RefleXion. JWW has accepted honoraria in the form of travel costs from Nanobiotix, RefleXion, Varian, Shandong University, The Korea Society of Radiology, Aileron Therapeutics and Ventana. JWW has the following patents; MP470 (amuvatinib), MRX34 regulation of PDL1, XRT technique to overcome immune resistance. MD Anderson Cancer Center has a trademark for RadScopal\u2122. The rest of the authors disclosed no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee at UT MD Anderson Cancer Center.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}