{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T04:21:44Z","timestamp":1768278104190,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Asia-Pac J Clncl Oncology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Although immune checkpoint inhibitors (ICPi) for salivary gland cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low\/high\u2010grade mucoepidermoid carcinoma (MEC<jats:sub>low\/high<\/jats:sub>). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ACC and MEC<jats:sub>high<\/jats:sub> showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEC<jats:sub>low<\/jats:sub> showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells in tumor and TMB (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.647). CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells in tumors showed a positive correlation with programmed cell death\u2010ligand 1 expression in tumor cells (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.513) and a weak positive correlation with CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> cells in tumors (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.399). However, no correlation was observed between CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells and CD204<jats:sup>+<\/jats:sup> cells in tumors (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u20100.049).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The TIME of ACC was the so\u2010called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEC<jats:sub>high<\/jats:sub> was the immune\u2010inflamed type, and this may support the rationale of ICPi for this pathological subtype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajco.14108","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T05:38:25Z","timestamp":1725514705000},"page":"779-788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer"],"prefix":"10.1111","volume":"20","author":[{"given":"Yoshiaki","family":"Nagatani","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Kiyota","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"},{"name":"Kobe University Hospital Cancer Center  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiji","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Teshima","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken\u2010Ichi","family":"Nibu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuko","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Genome Biology Kindai University Faculty of Medicine  Sayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuto","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Genome Biology Kindai University Faculty of Medicine  Sayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunotherapy (Kashiwa), Exploratory Oncology Research and Clinical Trial Center National Cancer Center  Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Nakatsura","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunotherapy (Kashiwa), Exploratory Oncology Research and Clinical Trial Center National Cancer Center  Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiki","family":"Ikarashi","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunotherapy (Kashiwa), Exploratory Oncology Research and Clinical Trial Center National Cancer Center  Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunotherapy (Kashiwa), Exploratory Oncology Research and Clinical Trial Center National Cancer Center  Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigehisa","family":"Kitano","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunotherapy Development, Center for Advanced Medical Development The Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine  Kobe Japan"},{"name":"Kobe University Hospital Cancer Center  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13952"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-022-01420-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyac008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-021-01581-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32409-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2111380"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00797-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.6083"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.6084"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.05.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.6092"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0244"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-020-0174-y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005320"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01679"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy495"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0768-9"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00763"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.15698\/cst2019.10.201"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.568931"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01628-y"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0360"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.6529"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx771"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01281-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0790"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102227"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1397"},{"issue":"7","key":"e_1_2_8_38_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-002591","article-title":"Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies","volume":"9","author":"Nishikawa H","year":"2021","journal-title":"J Immunother Cancer"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00500-y"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030675"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026982"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108330"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30445-9"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01661-z"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2005.05.010"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49215-9"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.24266"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2022.13333"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104143"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0398-5"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1713444"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2022-CT022"}],"container-title":["Asia-Pacific Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ajco.14108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:25:01Z","timestamp":1741749901000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ajco.14108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/ajco.14108"],"URL":"https:\/\/doi.org\/10.1111\/ajco.14108","archive":["Portico"],"relation":{},"ISSN":["1743-7555","1743-7563"],"issn-type":[{"value":"1743-7555","type":"print"},{"value":"1743-7563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]},"assertion":[{"value":"2023-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}