{"title":"不同亚型唾液腺癌的肿瘤免疫微环境各有特点。","authors":"Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Tomoo Itoh, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami","doi":"10.1111/ajco.14108","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Materials and methods: </strong>We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEC<sub>low/high</sub>). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing.</p><p><strong>Results: </strong>ACC and MEC<sub>high</sub> showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEC<sub>low</sub> showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3<sup>+</sup>CD8<sup>+</sup> T cells in tumor and TMB (r = 0.647). CD3<sup>+</sup>CD8<sup>+</sup> T cells in tumors showed a positive correlation with programmed cell death-ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3<sup>+</sup>CD4<sup>+</sup>Foxp3<sup>+</sup> cells in tumors (r = 0.399). However, no correlation was observed between CD3<sup>+</sup>CD8<sup>+</sup> T cells and CD204<sup>+</sup> cells in tumors (r = -0.049).</p><p><strong>Conclusion: </strong>The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEC<sub>high</sub> was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.</p>","PeriodicalId":8633,"journal":{"name":"Asia-Pacific journal of clinical oncology","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer.\",\"authors\":\"Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Tomoo Itoh, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami\",\"doi\":\"10.1111/ajco.14108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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.</p><p><strong>Materials and methods: </strong>We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEC<sub>low/high</sub>). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing.</p><p><strong>Results: </strong>ACC and MEC<sub>high</sub> showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEC<sub>low</sub> showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3<sup>+</sup>CD8<sup>+</sup> T cells in tumor and TMB (r = 0.647). CD3<sup>+</sup>CD8<sup>+</sup> T cells in tumors showed a positive correlation with programmed cell death-ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3<sup>+</sup>CD4<sup>+</sup>Foxp3<sup>+</sup> cells in tumors (r = 0.399). However, no correlation was observed between CD3<sup>+</sup>CD8<sup>+</sup> T cells and CD204<sup>+</sup> cells in tumors (r = -0.049).</p><p><strong>Conclusion: </strong>The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEC<sub>high</sub> was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.</p>\",\"PeriodicalId\":8633,\"journal\":{\"name\":\"Asia-Pacific journal of clinical oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asia-Pacific journal of clinical oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ajco.14108\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asia-Pacific journal of clinical oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ajco.14108","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：尽管针对唾液腺癌（SGC）的免疫检查点抑制剂（ICPi）已在临床试验中得到研究，但肿瘤免疫微环境（TIME）的细节仍不清楚。本研究旨在阐明SGC的TIME及其与肿瘤突变负荷（TMB）的关系，并探讨ICPi的适用性原理：我们选择了五种病理类型，即腺样囊性癌（ACC）、未特殊说明的腺癌（ANOS）、唾液腺导管癌（SDC）和低/高级别黏液表皮样癌（MEClow/high）。我们研究了每种病理类型的 TIME 和 TMB。TIME通过多重荧光免疫组化进行评估。TMB通过新一代测序法进行测量：结果：ACC 和 MEChigh 在肿瘤和基质中的免疫效应细胞和抑制细胞浸润分别最少和最多。ANOS、SDC和MEClow在肿瘤中显示出适度的免疫效应细胞浸润。相关分析表明，肿瘤中的 CD3+CD8+ T 细胞与 TMB 呈正相关（r = 0.647）。肿瘤中的 CD3+CD8+ T 细胞与肿瘤细胞中程序性细胞死亡配体 1 的表达呈正相关（r = 0.513），与肿瘤中的 CD3+CD4+Foxp3+ 细胞呈弱正相关（r = 0.399）。然而，肿瘤中的 CD3+CD8+ T 细胞与 CD204+ 细胞之间没有相关性（r = -0.049）：结论：ACC的TIME是所谓的免疫荒漠型，这可能解释了以往临床试验中ICPi反应不佳的机制。另一方面，MEChigh是免疫炎症型，这可能支持了ICPi用于该病理亚型的合理性。
Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer.
Aim: 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.
Materials and methods: We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing.
Results: ACC and MEChigh showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumors showed a positive correlation with programmed cell death-ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumors (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumors (r = -0.049).
Conclusion: The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.
期刊介绍：
Asia–Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia–Pacific region in relation to cancer treatment and care. The Journal is ideally positioned to receive publications that deal with diversity in cancer behavior, management and outcome related to ethnic, cultural, economic and other differences between populations. In addition to original articles, the Journal publishes reviews, editorials, letters to the Editor and short communications. Case reports are generally not considered for publication, only exceptional papers in which Editors find extraordinary oncological value may be considered for review. The Journal encourages clinical studies, particularly prospectively designed clinical trials.
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