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  • Title: Tumor infiltrating B-cells signal functional humoral immune responses in breast cancer.
    Author: Garaud S, Buisseret L, Solinas C, Gu-Trantien C, de Wind A, Van den Eynden G, Naveaux C, Lodewyckx JN, Boisson A, Duvillier H, Craciun L, Ameye L, Veys I, Paesmans M, Larsimont D, Piccart-Gebhart M, Willard-Gallo K.
    Journal: JCI Insight; 2019 Aug 13; 5(18):. PubMed ID: 31408436.
    Abstract:
    Tumor-infiltrating B-cells (TIL-B) in breast cancer (BC) have previously been associated with improved clinical outcomes; however, their role(s) in tumor immunity is not currently well known. This study confirms and extends the correlation between higher TIL-B densities and positive outcomes through an analysis of HER2-positive and triple-negative BC patients from the BIG 02-98 clinical trial (10yr mean follow-up). Fresh tissue analyses identify an increase in TIL-B density in untreated primary BC compared to normal breast tissues, which is associated with global, CD4+ and CD8+ TIL, higher tumor grades, higher proliferation and hormone receptor negativity. All B-cell differentiation stages are detectable but significant increases in memory TIL-B are consistently present. BC with higher infiltrates are specifically characterized by germinal center TIL-B, which in turn are correlated with TFH TIL and antibody-secreting TIL-B principally located in tertiary lymphoid structures. Some TIL-B also interact directly with tumor cells. Functional analyses reveal TIL-B are responsive to BCR stimulation ex vivo, express activation markers and produce cytokines and immunoglobulins despite reduced expression of the antigen-presenting molecules HLA-DR and CD40. Overall, these data support the concept that ongoing humoral immune responses are generated by TIL-B and help to generate effective anti-tumor immunity at the tumor site.
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