Tertiary lymphoid structures in cancer: maturation and induction

Tertiary lymphoid structures in cancer: maturation and induction

16 April 2024 | Yulu Chen, Yuhao Wu, Guorong Yan and Guolong Zhang
The article "Tertiary Lymphoid Structures in Cancer: Maturation and Induction" by Yulu Chen, Yuhao Wu, Guorong Yan, and Guolong Zhang provides a comprehensive overview of tertiary lymphoid structures (TLS) in cancer. TLS are organized aggregates of immune cells within the tumor microenvironment (TME), characterized by a central B cell zone surrounded by a rich T cell zone. The composition of TLS includes CD4+ T follicular helper (Tfh) cells, CD8+ cytotoxic T cells, CD4+ T helper 1 (Th1) cells, regulatory T cells (Tregs), and follicular dendritic cells (FDC). TLS can be immature or mature, with mature TLS exhibiting germinal centers (GC) and enhanced immune functionality. The formation of TLS is a response to chronic inflammation or tissue injury, involving interactions between lymphoid tissue inducer cells (LTI) and organizers (LTo), high endothelial venules (HEV) formation, and T/B compartmentalization. TLS detection relies on pathological diagnosis methods such as Hematoxylin and Eosin (HE) staining, immunohistochemistry (IHC), and immunofluorescence (IF). Gene signatures, including a 12-chemokines signature and a 29-gene TLS imprint signature, have been used to detect TLS. TLS are associated with better prognosis in various solid tumors, particularly in mature TLS. Clinical studies have shown that mature TLS are linked to improved response rates and survival in patients treated with immunotherapy, chemoradiotherapy, and other treatments. The induction of TLS by cancer treatments, such as immunotherapy, cytokines, agonists, inhibitors, and combination therapies, is discussed, highlighting their potential as predictive biomarkers and therapeutic targets. The article also explores the challenges and perspectives in understanding and utilizing TLS, including the need for further research on TLS maturity criteria, the differences between pre-existing and treatment-induced TLS, and the development of reliable in vitro systems and animal models. The authors emphasize the importance of TLS in cancer immunotherapy and the potential for personalized treatment strategies based on TLS formation and maturation.The article "Tertiary Lymphoid Structures in Cancer: Maturation and Induction" by Yulu Chen, Yuhao Wu, Guorong Yan, and Guolong Zhang provides a comprehensive overview of tertiary lymphoid structures (TLS) in cancer. TLS are organized aggregates of immune cells within the tumor microenvironment (TME), characterized by a central B cell zone surrounded by a rich T cell zone. The composition of TLS includes CD4+ T follicular helper (Tfh) cells, CD8+ cytotoxic T cells, CD4+ T helper 1 (Th1) cells, regulatory T cells (Tregs), and follicular dendritic cells (FDC). TLS can be immature or mature, with mature TLS exhibiting germinal centers (GC) and enhanced immune functionality. The formation of TLS is a response to chronic inflammation or tissue injury, involving interactions between lymphoid tissue inducer cells (LTI) and organizers (LTo), high endothelial venules (HEV) formation, and T/B compartmentalization. TLS detection relies on pathological diagnosis methods such as Hematoxylin and Eosin (HE) staining, immunohistochemistry (IHC), and immunofluorescence (IF). Gene signatures, including a 12-chemokines signature and a 29-gene TLS imprint signature, have been used to detect TLS. TLS are associated with better prognosis in various solid tumors, particularly in mature TLS. Clinical studies have shown that mature TLS are linked to improved response rates and survival in patients treated with immunotherapy, chemoradiotherapy, and other treatments. The induction of TLS by cancer treatments, such as immunotherapy, cytokines, agonists, inhibitors, and combination therapies, is discussed, highlighting their potential as predictive biomarkers and therapeutic targets. The article also explores the challenges and perspectives in understanding and utilizing TLS, including the need for further research on TLS maturity criteria, the differences between pre-existing and treatment-induced TLS, and the development of reliable in vitro systems and animal models. The authors emphasize the importance of TLS in cancer immunotherapy and the potential for personalized treatment strategies based on TLS formation and maturation.
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