{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:30:39Z","timestamp":1772800239143,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-182-011"],"award-info":[{"award-number":["MOST 109-2314-B-182-011"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2314-B-182-031"],"award-info":[{"award-number":["MOST 110-2314-B-182-031"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2314-B-182-003-MY3"],"award-info":[{"award-number":["MOST 110-2314-B-182-003-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumor cells express immune checkpoints to exhaust CD8+ T cells. Irradiation damages tumor cells and augments tumor immunotherapy in clinical applications. However, the radiotherapy-mediated molecular mechanism affecting CD8+ T cell activity remains elusive. We aimed to uncover the mechanism of radiotherapy augmenting cytotoxic CD8+ T cells in non-small-cell lung cancer (NSCLC). EGFR-positive NSCLC cell lines were co-cultured with CD8+ T cells from healthy volunteers. Tumor cell viability and apoptosis were consequently measured. IFN\u03b3 was identified secreted by CD8+ T cells and PBMCs. Therefore, RNAseq was used to screen the IFN\u03b3-mediated gene expression in A549 cells. The irradiation effect to IFN\u03b3-mediated gene expression was investigated using qPCR and western blots. We found that the co-culture of tumor cells stimulated the increase of granzyme B and IFN\u03b3 in CD8+ T, but A549 exhibited resistance against CD8+ T cytotoxicity compared to HCC827. Irradiation inhibited A549 proliferation and enhanced apoptosis, augmenting PBMCs-mediated cytotoxicity against A549. We found that IFN\u03b3 simultaneously increased phosphorylation on STAT1 and STAT3 in EGFR-positive lung cancer, resulting in overexpression of PD-L1 (p &lt; 0.05). In RNAseq analysis, MCL1 was identified and increased by the IFN\u03b3-STAT3 axis (p &lt; 0.05). We demonstrated that irradiation specifically inhibited phosphorylation on STAT1 and STAT3 in IFN\u03b3-treated A549, resulting in reductions of PD-L1 and MCL1 (both p &lt; 0.05). Moreover, knockdowns of STAT3 and MCL1 increased the PBMCs-mediated anti-A549 effect. This study demonstrated that A549 expressed MCL1 to resist CD8+ T cell-mediated tumor apoptosis. In addition, we found that irradiation suppressed IFN\u03b3-mediated STAT3 phosphorylation and PD-L1 and MCL1 expression, revealing a potential mechanism of radiotherapy augmenting immune surveillance.<\/jats:p>","DOI":"10.3390\/cells10102515","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:59:15Z","timestamp":1632391155000},"page":"2515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Irradiation Suppresses IFN\u03b3-Mediated PD-L1 and MCL1 Expression in EGFR-Positive Lung Cancer to Augment CD8+ T Cells Cytotoxicity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-0162","authenticated-orcid":false,"given":"Chun-I.","family":"Wang","sequence":"first","affiliation":[{"name":"Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University\/Chang Gung Memorial Hospital, Linkou 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Fang","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 104, Taiwan"},{"name":"Laboratory of Good Clinical Research Center, Department of Medical Research, Mackay Memorial Hospital, Tamsui District, New Taipei City 251, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3063-9927","authenticated-orcid":false,"given":"Zong-Lin","family":"Sie","sequence":"additional","affiliation":[{"name":"Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University\/Chang Gung Memorial Hospital, Linkou 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai-Sheng","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Cheng Hsin General Hospital, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Shan","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan 325, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-1798","authenticated-orcid":false,"given":"Chun-Chia","family":"Cheng","sequence":"additional","affiliation":[{"name":"Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University\/Chang Gung Memorial Hospital, Linkou 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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