The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Abstract Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the imp...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02340-2 |
| _version_ | 1811290427707359232 |
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| author | Dong Liu Lara Rosaline Heij Zoltan Czigany Edgar Dahl Sven Arke Lang Tom Florian Ulmer Tom Luedde Ulf Peter Neumann Jan Bednarsch |
| author_facet | Dong Liu Lara Rosaline Heij Zoltan Czigany Edgar Dahl Sven Arke Lang Tom Florian Ulmer Tom Luedde Ulf Peter Neumann Jan Bednarsch |
| author_sort | Dong Liu |
| collection | DOAJ |
| description | Abstract Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients. In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA. In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translational data is needed to fully unravel the importance of TILs in the treatment of CCA. |
| first_indexed | 2024-04-13T04:12:41Z |
| format | Article |
| id | doaj.art-ec66657d903d40aea7cb9620a8d5976b |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T04:12:41Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-ec66657d903d40aea7cb9620a8d5976b2022-12-22T03:03:04ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-04-0141111810.1186/s13046-022-02340-2The role of tumor-infiltrating lymphocytes in cholangiocarcinomaDong Liu0Lara Rosaline Heij1Zoltan Czigany2Edgar Dahl3Sven Arke Lang4Tom Florian Ulmer5Tom Luedde6Ulf Peter Neumann7Jan Bednarsch8Department of Surgery and Transplantation, University Hospital RWTH AachenDepartment of Surgery and Transplantation, University Hospital RWTH AachenDepartment of Surgery and Transplantation, University Hospital RWTH AachenInstitute of Pathology, University Hospital RWTH AachenDepartment of Surgery and Transplantation, University Hospital RWTH AachenDepartment of Surgery and Transplantation, University Hospital RWTH AachenDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Heinrich Heine University DuesseldorfDepartment of Surgery and Transplantation, University Hospital RWTH AachenDepartment of Surgery and Transplantation, University Hospital RWTH AachenAbstract Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients. In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA. In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translational data is needed to fully unravel the importance of TILs in the treatment of CCA.https://doi.org/10.1186/s13046-022-02340-2Cholangiocarcinoma, Tumor-infiltrating lymphocytes (TIL)Molecular pathogenesisOncological prognosisImmunotherapySystematic review |
| spellingShingle | Dong Liu Lara Rosaline Heij Zoltan Czigany Edgar Dahl Sven Arke Lang Tom Florian Ulmer Tom Luedde Ulf Peter Neumann Jan Bednarsch The role of tumor-infiltrating lymphocytes in cholangiocarcinoma Journal of Experimental & Clinical Cancer Research Cholangiocarcinoma, Tumor-infiltrating lymphocytes (TIL) Molecular pathogenesis Oncological prognosis Immunotherapy Systematic review |
| title | The role of tumor-infiltrating lymphocytes in cholangiocarcinoma |
| title_full | The role of tumor-infiltrating lymphocytes in cholangiocarcinoma |
| title_fullStr | The role of tumor-infiltrating lymphocytes in cholangiocarcinoma |
| title_full_unstemmed | The role of tumor-infiltrating lymphocytes in cholangiocarcinoma |
| title_short | The role of tumor-infiltrating lymphocytes in cholangiocarcinoma |
| title_sort | role of tumor infiltrating lymphocytes in cholangiocarcinoma |
| topic | Cholangiocarcinoma, Tumor-infiltrating lymphocytes (TIL) Molecular pathogenesis Oncological prognosis Immunotherapy Systematic review |
| url | https://doi.org/10.1186/s13046-022-02340-2 |
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