Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer
The omentum is a common site of peritoneal metastasis in various cancers, including gastric cancer. It contains immune cell aggregates known as milky spots, which provide a microenvironment for peritoneal immunity by regulating innate and adaptive immune responses. In this study, we investigated gen...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521278/full |
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| author | Yasunobu Mano Yasunobu Mano Yuka Igarashi Yuka Igarashi Keisuke Komori Keisuke Komori Itaru Hashimoto Itaru Hashimoto Hayato Watanabe Kosuke Takahashi Kazuki Kano Hirohito Fujikawa Takanobu Yamada Hidetomo Himuro Hidetomo Himuro Taku Kouro Taku Kouro Feifei Wei Feifei Wei Kayoko Tsuji Kayoko Tsuji Shun Horaguchi Shun Horaguchi Shun Horaguchi Mitsuru Komahashi Mitsuru Komahashi Mitsuru Komahashi Takashi Oshima Tetsuro Sasada Tetsuro Sasada |
| author_facet | Yasunobu Mano Yasunobu Mano Yuka Igarashi Yuka Igarashi Keisuke Komori Keisuke Komori Itaru Hashimoto Itaru Hashimoto Hayato Watanabe Kosuke Takahashi Kazuki Kano Hirohito Fujikawa Takanobu Yamada Hidetomo Himuro Hidetomo Himuro Taku Kouro Taku Kouro Feifei Wei Feifei Wei Kayoko Tsuji Kayoko Tsuji Shun Horaguchi Shun Horaguchi Shun Horaguchi Mitsuru Komahashi Mitsuru Komahashi Mitsuru Komahashi Takashi Oshima Tetsuro Sasada Tetsuro Sasada |
| author_sort | Yasunobu Mano |
| collection | DOAJ |
| description | The omentum is a common site of peritoneal metastasis in various cancers, including gastric cancer. It contains immune cell aggregates known as milky spots, which provide a microenvironment for peritoneal immunity by regulating innate and adaptive immune responses. In this study, we investigated gene expression profiles in cells from omental milky spots of patients with gastric cancer (n = 37) by RNA sequencing analysis and classified the patients into four groups (G1-4). Notably, significant differences were observed between the groups in terms of macroscopic type, lymphatic invasion, venous invasion, and pathological stage (pStage). G3, which was enriched in genes related to acquired immunity, showed earlier tumor stages (macroscopic type 0, Ly0, V0, and pStage I) and a better prognosis. In contrast, G4 showed enrichment of genes related to neutrophils and innate immunity; G1 and G2 showed no enrichment of innate or adaptive immune-related genes, suggesting an immune desert microenvironment. Cytometric analysis revealed significantly more T and B cells and fewer neutrophils in G3. Accordingly, the immune microenvironment in omental milky spots may vary depending on the stage of gastric cancer progression. When univariate Cox proportional hazards regression models were used to search for prognostically relevant genes specific to G3, 23 potential prognostic genes were identified as common genes associated with relapse-free survival and overall survival. In addition, the multivariate Cox proportional hazards model using these prognostic genes and clinicopathological information showed that combining the B cell marker CD19 and Ly had a high predictive accuracy for prognosis. Based on this study’s results, it is possible that tumor progression, such as lymphatic and/or venous infiltration of tumor cells, may affect the immune cell composition and proportions in omental milky spots of patients with gastric cancer and analysis of gene expression in omental milky spots may help to predict gastric cancer prognosis. |
| format | Article |
| id | doaj-art-286e1f4f0f754272a81c272f28f43eaa |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-286e1f4f0f754272a81c272f28f43eaa2025-01-30T06:22:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15212781521278Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancerYasunobu Mano0Yasunobu Mano1Yuka Igarashi2Yuka Igarashi3Keisuke Komori4Keisuke Komori5Itaru Hashimoto6Itaru Hashimoto7Hayato Watanabe8Kosuke Takahashi9Kazuki Kano10Hirohito Fujikawa11Takanobu Yamada12Hidetomo Himuro13Hidetomo Himuro14Taku Kouro15Taku Kouro16Feifei Wei17Feifei Wei18Kayoko Tsuji19Kayoko Tsuji20Shun Horaguchi21Shun Horaguchi22Shun Horaguchi23Mitsuru Komahashi24Mitsuru Komahashi25Mitsuru Komahashi26Takashi Oshima27Tetsuro Sasada28Tetsuro Sasada29Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Surgery, Yokohama City University, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Surgery, Yokohama City University, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDepartment of Pediatric Surgery, Nihon University School of Medicine, Tokyo, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanDepartment of Pediatric Surgery, Nihon University School of Medicine, Tokyo, JapanDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, JapanDivision of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, JapanCancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama, JapanThe omentum is a common site of peritoneal metastasis in various cancers, including gastric cancer. It contains immune cell aggregates known as milky spots, which provide a microenvironment for peritoneal immunity by regulating innate and adaptive immune responses. In this study, we investigated gene expression profiles in cells from omental milky spots of patients with gastric cancer (n = 37) by RNA sequencing analysis and classified the patients into four groups (G1-4). Notably, significant differences were observed between the groups in terms of macroscopic type, lymphatic invasion, venous invasion, and pathological stage (pStage). G3, which was enriched in genes related to acquired immunity, showed earlier tumor stages (macroscopic type 0, Ly0, V0, and pStage I) and a better prognosis. In contrast, G4 showed enrichment of genes related to neutrophils and innate immunity; G1 and G2 showed no enrichment of innate or adaptive immune-related genes, suggesting an immune desert microenvironment. Cytometric analysis revealed significantly more T and B cells and fewer neutrophils in G3. Accordingly, the immune microenvironment in omental milky spots may vary depending on the stage of gastric cancer progression. When univariate Cox proportional hazards regression models were used to search for prognostically relevant genes specific to G3, 23 potential prognostic genes were identified as common genes associated with relapse-free survival and overall survival. In addition, the multivariate Cox proportional hazards model using these prognostic genes and clinicopathological information showed that combining the B cell marker CD19 and Ly had a high predictive accuracy for prognosis. Based on this study’s results, it is possible that tumor progression, such as lymphatic and/or venous infiltration of tumor cells, may affect the immune cell composition and proportions in omental milky spots of patients with gastric cancer and analysis of gene expression in omental milky spots may help to predict gastric cancer prognosis.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521278/fullomental milky spotsgastric canceradaptive immune responseslymphatic invasionimmune microenvironment |
| spellingShingle | Yasunobu Mano Yasunobu Mano Yuka Igarashi Yuka Igarashi Keisuke Komori Keisuke Komori Itaru Hashimoto Itaru Hashimoto Hayato Watanabe Kosuke Takahashi Kazuki Kano Hirohito Fujikawa Takanobu Yamada Hidetomo Himuro Hidetomo Himuro Taku Kouro Taku Kouro Feifei Wei Feifei Wei Kayoko Tsuji Kayoko Tsuji Shun Horaguchi Shun Horaguchi Shun Horaguchi Mitsuru Komahashi Mitsuru Komahashi Mitsuru Komahashi Takashi Oshima Tetsuro Sasada Tetsuro Sasada Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer Frontiers in Immunology omental milky spots gastric cancer adaptive immune responses lymphatic invasion immune microenvironment |
| title | Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| title_full | Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| title_fullStr | Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| title_full_unstemmed | Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| title_short | Characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| title_sort | characteristics and clinical significance of immune cells in omental milky spots of patients with gastric cancer |
| topic | omental milky spots gastric cancer adaptive immune responses lymphatic invasion immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521278/full |
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