The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors
BackgroundPrimary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance rem...
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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.2025.1536722/full |
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| author | Jiajun Zhou Jiajun Zhou Wenhao An Lei Guan Lei Guan Jinyu Shi Qiaozhen Qin Shuai Zhong Zheng Huang Rui Liu Chenxing Wu Zhong Ma Xueling Qi Xiaoxia Jiang Yan Wang Shouwei Li |
| author_facet | Jiajun Zhou Jiajun Zhou Wenhao An Lei Guan Lei Guan Jinyu Shi Qiaozhen Qin Shuai Zhong Zheng Huang Rui Liu Chenxing Wu Zhong Ma Xueling Qi Xiaoxia Jiang Yan Wang Shouwei Li |
| author_sort | Jiajun Zhou |
| collection | DOAJ |
| description | BackgroundPrimary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance remain poorly understood.MethodsThis study included 93 paraffin-embedded tissue samples from 90 patients diagnosed with CNS GCTs. Immunohistochemistry and immunofluorescence staining were used to assess the infiltration patterns of T cell subsets (CD3+, CD4+, CD8+, Foxp3+) and the expression levels of immune checkpoints (CTLA-4, PD-1, PD-L1). Additionally, the study explored the relationship between these immune features and the patient’s clinical characteristics and prognosis.ResultsThe study revealed that germinomas exhibited significantly higher infiltration of CD4+ and Foxp3+ T cells compared to non-germinomatous GCTs (NGGCTs). Additionally, CTLA-4 expression was detected in 58.06% of cases, while PD-1 and PD-L1 were expressed in over 90%, with higher CTLA-4 levels in germinomas and elevated PD-L1 levels in NGGCTs. T cell infiltration was positively correlated with immune checkpoint expression, particularly in germinomas. The results also highlighted the strong immunosuppressive nature of the CNS GCTs’ tumor microenvironment. Furthermore, T cell infiltration and immune checkpoint expression were closely associated with clinical characteristics and prognosis. Notably, PD-1 expression was identified as an independent prognostic factor for progression-free survival (PFS) and recurrence-free survival (RFS).ConclusionOur study highlighted the distinct characteristics of T cell infiltration and the significant expression of immune checkpoints in CNS GCTs, revealing the highly heterogeneous and immunosuppressive nature of the tumor microenvironment. PD-1 expression was identified as an independent prognostic predictor, offering a foundation for enhancing risk stratification in CNS GCT patients. These findings also support the potential for future clinical applications of immune checkpoint inhibitors, such as PD-1 monoclonal antibodies. |
| format | Article |
| id | doaj-art-de97b0d865d04880a9abbb18fb2532d9 |
| 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-de97b0d865d04880a9abbb18fb2532d92025-01-31T06:39:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15367221536722The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumorsJiajun Zhou0Jiajun Zhou1Wenhao An2Lei Guan3Lei Guan4Jinyu Shi5Qiaozhen Qin6Shuai Zhong7Zheng Huang8Rui Liu9Chenxing Wu10Zhong Ma11Xueling Qi12Xiaoxia Jiang13Yan Wang14Shouwei Li15Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neuroimmunology, Beijing Institute of Basic Medical Sciences, Beijing, ChinaDepartment of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, ChinaBackgroundPrimary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance remain poorly understood.MethodsThis study included 93 paraffin-embedded tissue samples from 90 patients diagnosed with CNS GCTs. Immunohistochemistry and immunofluorescence staining were used to assess the infiltration patterns of T cell subsets (CD3+, CD4+, CD8+, Foxp3+) and the expression levels of immune checkpoints (CTLA-4, PD-1, PD-L1). Additionally, the study explored the relationship between these immune features and the patient’s clinical characteristics and prognosis.ResultsThe study revealed that germinomas exhibited significantly higher infiltration of CD4+ and Foxp3+ T cells compared to non-germinomatous GCTs (NGGCTs). Additionally, CTLA-4 expression was detected in 58.06% of cases, while PD-1 and PD-L1 were expressed in over 90%, with higher CTLA-4 levels in germinomas and elevated PD-L1 levels in NGGCTs. T cell infiltration was positively correlated with immune checkpoint expression, particularly in germinomas. The results also highlighted the strong immunosuppressive nature of the CNS GCTs’ tumor microenvironment. Furthermore, T cell infiltration and immune checkpoint expression were closely associated with clinical characteristics and prognosis. Notably, PD-1 expression was identified as an independent prognostic factor for progression-free survival (PFS) and recurrence-free survival (RFS).ConclusionOur study highlighted the distinct characteristics of T cell infiltration and the significant expression of immune checkpoints in CNS GCTs, revealing the highly heterogeneous and immunosuppressive nature of the tumor microenvironment. PD-1 expression was identified as an independent prognostic predictor, offering a foundation for enhancing risk stratification in CNS GCT patients. These findings also support the potential for future clinical applications of immune checkpoint inhibitors, such as PD-1 monoclonal antibodies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1536722/fullgerm cell tumortumor microenvironmenttumor-infiltrating lymphocyte (TILs)immune checkpointFoxp3CTLA-4 |
| spellingShingle | Jiajun Zhou Jiajun Zhou Wenhao An Lei Guan Lei Guan Jinyu Shi Qiaozhen Qin Shuai Zhong Zheng Huang Rui Liu Chenxing Wu Zhong Ma Xueling Qi Xiaoxia Jiang Yan Wang Shouwei Li The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors Frontiers in Immunology germ cell tumor tumor microenvironment tumor-infiltrating lymphocyte (TILs) immune checkpoint Foxp3 CTLA-4 |
| title | The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| title_full | The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| title_fullStr | The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| title_full_unstemmed | The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| title_short | The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| title_sort | clinical significance of t cell infiltration and immune checkpoint expression in central nervous system germ cell tumors |
| topic | germ cell tumor tumor microenvironment tumor-infiltrating lymphocyte (TILs) immune checkpoint Foxp3 CTLA-4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1536722/full |
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