Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
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Characterization of tumor-infiltrating B cells in solid tumors
Current immunotherapies focus mostly on immune cells designated as CD8+ cytotoxic T cells to fight cancer. Despite growing appreciation to the role of B cells in solid tumor microenvironments, most of the immune checkpoint blockade therapy targets are developed with the purpose to act on T cells and induce their activation. Up to now, a heterogenous impact has been ascribed to B cells infiltrating solid tumors. The presence of B cells within tumors has been correlated with improved patient survival in several studies, however, there are also investigations which describe pro-tumor roles of B cells and severe disease progression. These varying observations depend on the tumor entity and B cell subset investigated, but the exact underlying mechanisms and regulations are still only poorly understood and remain to be fully elucidated. The aim of this project is to characterize tumor infiltrating B cells phenotypically in solid tumor entities. For this purpose, the MACSima technology is used to investigate the marker expression pattern of B cells present in solid tumors in context to their spatial localization. B cells could be detected in 21% of the samples screened. Here, tertiary lymphoid structures (TLS) like structures were identified consisting of mainly B and T cells, but also CD64+ macrophages, high endothelial venules and CD21+ follicular dendritic cells. Even though no new B cell subset could be identified to this point, the interesting observation could be made that the B cells within the TLS like structure show a prevalence of a memory B cell phenotype. In line with that, similar observation were made by flow cytometry analysis of freshly dissociated solid tumor. Interestingly, additional to that, a distinctive CD138+CD38+ plasma cell population was detected in the surrounding of the TLS like structure within the tumor by MACSima which could as well be validated by flow cytometric and RNA sequencing analysis of dissociated tumor samples. Observation of many memory B cells and plasma cells strengthens the ...
Characterization of tumor-infiltrating B cells in solid tumors
Current immunotherapies focus mostly on immune cells designated as CD8+ cytotoxic T cells to fight cancer. Despite growing appreciation to the role of B cells in solid tumor microenvironments, most of the immune checkpoint blockade therapy targets are developed with the purpose to act on T cells and induce their activation. Up to now, a heterogenous impact has been ascribed to B cells infiltrating solid tumors. The presence of B cells within tumors has been correlated with improved patient survival in several studies, however, there are also investigations which describe pro-tumor roles of B cells and severe disease progression. These varying observations depend on the tumor entity and B cell subset investigated, but the exact underlying mechanisms and regulations are still only poorly understood and remain to be fully elucidated. The aim of this project is to characterize tumor infiltrating B cells phenotypically in solid tumor entities. For this purpose, the MACSima technology is used to investigate the marker expression pattern of B cells present in solid tumors in context to their spatial localization. B cells could be detected in 21% of the samples screened. Here, tertiary lymphoid structures (TLS) like structures were identified consisting of mainly B and T cells, but also CD64+ macrophages, high endothelial venules and CD21+ follicular dendritic cells. Even though no new B cell subset could be identified to this point, the interesting observation could be made that the B cells within the TLS like structure show a prevalence of a memory B cell phenotype. In line with that, similar observation were made by flow cytometry analysis of freshly dissociated solid tumor. Interestingly, additional to that, a distinctive CD138+CD38+ plasma cell population was detected in the surrounding of the TLS like structure within the tumor by MACSima which could as well be validated by flow cytometric and RNA sequencing analysis of dissociated tumor samples. Observation of many memory B cells and plasma cells strengthens the ...
Characterization of tumor-infiltrating B cells in solid tumors
Singh, Aparajita (Autor:in) / Küppers, Ralf
31.10.2023
Hochschulschrift
Elektronische Ressource
Englisch