Follicular helper T cells: implications in neoplastic hematopathology

A distinct subset of T helper cells, named follicular T helper cells (TFH), has been recently described. TFH cells are characterized by their homing capacities in the germinal centers of B-cell follicles where they interact with B cells, supporting B-cell survival and antibody responses. TFH cells can be identified by the expression of several markers including the chemokine CXCL13, the costimulatory molecules PD1 and inducible costimulator, and the transcription factor BCL6. They appear to be relevant markers for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and have helped to recognize subsets of peripheral T-cell lymphoma, not otherwise specified, with nodal or cutaneous presentation expressing TFH antigens that might be related to AITL. In B-cell neoplasms, TFH cells are present within the microenvironment of nodular lymphocyte-predominant Hodgkin lymphoma and follicular lymphoma, where they likely support the growth of neoplastic germinal center-derived B cells. Interestingly, the amount of PD1+ cells in the neoplastic follicles might have a favorable impact on the outcome of follicular lymphoma patients. Altogether, the availability of antibodies directed to TFH-associated molecules has important diagnostic and prognostic implications in hematopathology. In addition, TFH cells could represent interesting targets in TFH-derived lymphomas such as AITL, or in some B-cell neoplasms where they act as part of the tumor microenvironment.