T follicular helper cells (T FH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with T FH cell infiltration and improved survival in human cancer. Although human T FH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5–) T FH cells, here named T FH X13 cells, in promoting local memory B cell differentiation. T FH X13 cells potentially trigger tertiary lymphoid structure formation and thereby generate germinal center B cell responses at the tumor site. Follicular DCs are not potent CXCL13 producers in breast tumor tissues. We used the T FH cell markers PD-1 and ICOS to identify distinct effector and regulatory CD4+ T cell subpopulations in breast tumors. T FH X13 cells are an important component of the PD-1 hi ICOS int effector subpopulation and coexpanded with PD-1 int ICOS hi FOXP3 hi Tregs. IL2 deprivation induces CXCL13 expression in vitro with a synergistic effect from TGFβ1, providing insight into T FH X13 cell differentiation in response to Treg accumulation, similar to conventional T FH cell responses. Our data suggest that human T FH X13 cell differentiation may be a key factor in converting Treg-mediated immune suppression to de novo activation of adaptive antitumor humoral responses in the chronic inflammatory breast cancer microenvironment.