PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers
Background: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration...
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| Format: | Article |
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Elsevier
2023-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558623000453 |
| _version_ | 1827856307157204992 |
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| author | Wen-Jie Ma Zheng-Hua Li Zhen-Ru Wu Fei Liu Jun-Ke Wang Yu-Jun Shi Yan-Wen Jin Fu-Yu Li |
| author_facet | Wen-Jie Ma Zheng-Hua Li Zhen-Ru Wu Fei Liu Jun-Ke Wang Yu-Jun Shi Yan-Wen Jin Fu-Yu Li |
| author_sort | Wen-Jie Ma |
| collection | DOAJ |
| description | Background: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8+ T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs. Methods: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8+ T lymphocyte infiltration is affected by the tumor microbiome of BTCs. Results: We enrolled 32 patients with resected BTCs. The high CD8+ lymphocyte-infiltration (CD8hi) group had four significantly enriched taxa, and in the low CD8+ lymphocyte-infiltration (CD8low) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8+ lymphocyte infiltration in BTCs. Conclusions: The tumor microbiome is related to CD8+ T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8+ T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis. |
| first_indexed | 2024-03-12T12:23:48Z |
| format | Article |
| id | doaj.art-8ec6d8c1ba7546e09c5d8ab3c17edf1c |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-03-12T12:23:48Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-8ec6d8c1ba7546e09c5d8ab3c17edf1c2023-08-30T05:50:13ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862023-09-0143100920PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancersWen-Jie Ma0Zheng-Hua Li1Zhen-Ru Wu2Fei Liu3Jun-Ke Wang4Yu-Jun Shi5Yan-Wen Jin6Fu-Yu Li7Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, ChinaDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaInstitute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, ChinaDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, ChinaInstitute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, ChinaDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, China; Corresponding authors at: Chengdu, China. No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China.Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, China; Corresponding authors at: Chengdu, China. No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China.Background: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8+ T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs. Methods: Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8+ T lymphocyte infiltration is affected by the tumor microbiome of BTCs. Results: We enrolled 32 patients with resected BTCs. The high CD8+ lymphocyte-infiltration (CD8hi) group had four significantly enriched taxa, and in the low CD8+ lymphocyte-infiltration (CD8low) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8hi group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8hi group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8+ lymphocyte infiltration in BTCs. Conclusions: The tumor microbiome is related to CD8+ T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8+ T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis.http://www.sciencedirect.com/science/article/pii/S1476558623000453Bile tract cancersTumor microbiomeCD8+ T lymphocyteMyeloid-derived suppressor cellPhosphatidylinositol 3-kinase activity |
| spellingShingle | Wen-Jie Ma Zheng-Hua Li Zhen-Ru Wu Fei Liu Jun-Ke Wang Yu-Jun Shi Yan-Wen Jin Fu-Yu Li PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers Neoplasia: An International Journal for Oncology Research Bile tract cancers Tumor microbiome CD8+ T lymphocyte Myeloid-derived suppressor cell Phosphatidylinositol 3-kinase activity |
| title | PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers |
| title_full | PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers |
| title_fullStr | PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers |
| title_full_unstemmed | PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers |
| title_short | PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8+ T lymphocyte infiltration in bile tract cancers |
| title_sort | pi3k ccl2 ccr2 mdscs axis a potential pathway for tumor clostridia promoted cd 8 t lymphocyte infiltration in bile tract cancers |
| topic | Bile tract cancers Tumor microbiome CD8+ T lymphocyte Myeloid-derived suppressor cell Phosphatidylinositol 3-kinase activity |
| url | http://www.sciencedirect.com/science/article/pii/S1476558623000453 |
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