Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer. (April 2020)

• Record Type: Journal Article
• Authors: Sautès-Fridman, Catherine; Verneau, Johanna; Sun, Cheng-Ming; Moreira, Marco; Chen, Tom Wei-Wu; Meylan, Maxime; Petitprez, Florent; Fridman, Wolf Herman
• Is Part Of: Seminars in immunology. Volume 48(2020)
• Publication Date: 2020-04
• Subjects: TLS tertiary lymphoid structures -- BC breast carcinoma -- CRC colorectal carcinoma -- GBM glioblastoma -- ccRCC clear cell renal cell cancer -- HCC Hepatocellular carcinoma -- NSCLC non squamous cell lung cancer -- STS soft tissue sarcoma -- GIST gastrointestinal stromal tumors -- RCC renal cell cancer -- SCLC Squamous cell lung cancer -- TNBC triple negative breast cancer -- FRC follicular reticular cells -- FDC Follicular Dendritic cells; Tertiary lymphoid structures -- B cells -- Adaptive anti-tumor response -- Prognosis -- Clinical outcome -- Immunotherapy; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Immunity -- Periodicals; Immunologie -- Périodiques; Electronic journals; 616.079
• DOI: 10.1016/j.smim.2020.101406
• Languages: English
• ISSNs: 1044-5323

Abstract

Highlights: TLS are active sites for the generation and activation of adaptive immune responses in tumors. B cells and TLS have a favorable impact on patient's prognosis and response to immunotherapy. The impact of the T cells infiltrate on the prognostic value of B cells is tumor dependent. Chemotherapy and immunotherapy induce TLS formation. B cells may function via antigen-presentation, antibody production and generation of memory cells. Abstract: Tumors progression is under the control of a heterogeneous microenvironment composed of immune cells, fibroblasts, blood and lymphatic vessels, in which T cells have been demonstrated to be major actors, through their cytotoxic and cytokine producing effector functions and their long term memory that protects against metastasis. In this scenario, lessons from mouse models taught that B cells exert a protumoral role, via macrophage-dependent activation of inflammation. However, it became progressively evident from studies in patients with human cancers that the anti-tumor responses can be generated and controlled in tertiary lymphoid structures (TLS) that concentrate most of the intratumoral B cells and where B cells can differentiate into plasma cells and memory cells. Furthermore, recent studies demonstrated that the presence in tumors of B cells and TLS are associated with favorable outcome in patients treated by immunotherapy, unraveling TLS as a new predictive marker of anti-tumor response human cancers. This review encompasses the characteristics and functions of TLS and of B cells in human tumors, their prognostic and theranostic impact and summarizes the mouse models used to induce TLS neogenesis in tumors.