{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T01:35:09Z","timestamp":1780364109512,"version":"3.54.1"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K15076"],"award-info":[{"award-number":["JP18K15076"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR\u2010TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death\u2010ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR\u2010TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR\u2010TKI resistance and lymphocyte infiltration, before and after acquiring EGFR\u2010TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by <jats:italic>in vitro<\/jats:italic> studies, using miRNA PCR arrays. Subsequently, we transfected miRNA\u20101 (miR\u20101), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR\u20101 on EGFR\u2010TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8\u2010positive T cells were significantly decreased after development of EGFR\u2010TKI resistance. <jats:italic>In vitro<\/jats:italic> studies revealed that miR\u20101 significantly inhibited EGFR\u2010TKI effect and induction of cytokines, such as C\u2010C motif chemokine ligand 5 and C\u2010X\u2010C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR\u20101 might suppress the TIME, following development of EGFR\u2010TKI resistance. Therefore, miR\u20101 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR\u2010TKI resistance.<\/jats:p>","DOI":"10.1002\/cam4.3639","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T11:19:24Z","timestamp":1607685564000},"page":"718-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Suppression of tumor immune microenvironment via microRNA\u20101 after epidermal growth factor receptor\u2010tyrosine kinase inhibitor resistance acquirement in lung adenocarcinoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-6949","authenticated-orcid":false,"given":"Sachiko","family":"Kawana","sequence":"first","affiliation":[{"name":"Department of Pathology Tohoku University School of Medicine Miyagi Japan"},{"name":"Department of Respiratory Medicine Sendai Kousei Hospital 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