{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:16:16Z","timestamp":1770819376781,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T00:00:00Z","timestamp":1581897600000},"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":["JP1426830111"],"award-info":[{"award-number":["JP1426830111"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Currently, anticancer immunotherapy based on PD\u20101\/PD\u2010L1 blockade with immune checkpoint inhibitors (ICIs) is being used as a standard therapy for non\u2010small cell lung cancer (NSCLC). However, more effective treatments are required as these tumors are often resistant and refractory. Here, we aimed to determine the effects of immunomodulatory oligodeoxynucleotides (ODNs) in terms of the presence or absence of CpG motifs and the number of consecutive guanosines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Western blots were used to measure the molecules which regulate the expression of PD\u2010L1 in human lung cancer cell lines after incubation with several cytokines and ODNs. The expression of PD\u2010L1 and \u03b22\u2010microglobulin (\u03b22\u2010MG) on A549 cells, and IFN\u2010\u03b3\u2010induced apoptosis with ODNs were examined by flow cytometry. The relationship between IFN\u2010\u03b3 receptor and ODN was analyzed by ELISA and immunofluorescence chemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results verified that A\u2010CpG ODNs suppress the upregulation of IFN\u2010\u03b3\u2010induced PD\u2010L1 and \u03b22\u2010MG expression. In addition, we found that ODNs with six or more consecutive guanosines (ODNs with poly\u2010G sequences) may competitively inhibit the IFN\u2010\u03b3 receptor and abolish the effect of IFN\u2010\u03b3, thereby suppressing apoptosis and indoleamine 2,3\u2010dioxygenase 1 expression in human lung cancer cells. The tumor microenvironment regulates whether this action will promote or suppress tumor immunity. Thus, in immunotherapy with CpG ODNs, it is essential to consider the effect of ODNs with poly\u2010G sequences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that ODNs containing six or more consecutive guanosines may inhibit the binding of IFN\u2010\u03b3 to IFN\u2010\u03b3 receptor. However, it does not directly show that ODNs containing six or more consecutive guanosines competitively inhibit the IFN\u2010\u03b3 receptor, and further studies are warranted to confirm this finding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>\n<jats:bold>Significant findings of the study:<\/jats:bold> Oligodeoxynucleotides with a contiguous sequence of six or more guanosines may competitively inhibit the IFN\u2010\u03b3 receptor and abolish the action of IFN\u2010\u03b3. This may suppress IFN\u2010\u03b3\u2010induced apoptosis and indoleamine\u20102,3\u2010dioxygenase\u20101 expression in human lung cancer cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\n<jats:bold>What this study adds:<\/jats:bold> A\u2010CpG and poly\u2010G ODN may overcome tolerance if the cause of ICI tolerance is high IDO expression. However, IFN\u2010\u03b3 also has the effect of suppressing apoptosis of cancer cells, and it is necessary to identify the cause of resistance.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13351","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T02:55:12Z","timestamp":1581994512000},"page":"983-992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Class A CpG oligodeoxynucleotide inhibits IFN\u2010\u03b3\u2010induced signaling and apoptosis in lung cancer"],"prefix":"10.1111","volume":"11","author":[{"given":"Shuhei","family":"Teranishi","sequence":"first","affiliation":[{"name":"Department of Pulmonology Yokohama City University Graduate School of Medicine  Yokohama 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