TY - JOUR AU - Garaud, Soizic AU - Buisseret, Laurence AU - Solinas, Cinzia AU - Gu-Trantien, Chunyan AU - de Wind, Alexandre AU - Van den Eynden, Gert AU - Naveaux, Celine AU - Lodewyckx, Jean-Nicolas AU - Boisson, Anaïs AU - Duvillier, Hughes AU - Craciun, Ligia AU - Ameye, Lieveke AU - Veys, Isabelle AU - Paesmans, Marianne AU - Larsimont, Denis AU - Piccart-Gebhart, Martine AU - Willard-Gallo, Karen T1 - Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer PY - 2019/09/19/ AB - Tumor-infiltrating B cells (TIL-B) in breast cancer (BC) have previously been associated with improved clinical outcomes; however, their roles in tumor immunity are not currently well known. This study confirms and extends the correlation between higher TIL-B densities and positive outcomes through an analysis of HER2+ and triple-negative BC patients from the BIG 02-98 clinical trial (10-year median follow-up). Fresh tissue analyses identify an increase in TIL-B density in untreated primary BC compared with normal breast tissues, which is associated with global, CD4+, and CD8+ tumor infiltrating lymphocytes (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 T follicular helper (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 that TIL-B are responsive to B cell receptor (BCR) stimulation ex vivo, express activation markers, and produce cytokines and Igs 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 promote effective antitumor immunity at the tumor site. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.129641 VL - 4 IS - 18 UR - https://doi.org/10.1172/jci.insight.129641 PB - The American Society for Clinical Investigation ER -