Targeting JMJD1C to selectively disrupt tumor T cell fitness enhances antitumor immunity.

Regulatory T (T) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving T cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral T cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral T cell-specific epigenetic regulators have been unexplored.

Histone methyltransferase Nsd2 is required for follicular helper T cell differentiation.

Follicular helper T (Tfh) cells provide essential help for humoral immune response. Transcriptional factor Bcl6 is the master regulator for Tfh generation and is induced very early after T cell activation in a CD28-dependent manner, but how CD28 signal promotes Bcl6 early expression remains unknown. Here we found that CD28 signal quickly induces expression of the H3K36me2 methytransferase Nsd2, which is required for Bcl6 expression as early as the first cell division after T cell activation.

Methyltransferase Nsd2 Ensures Germinal Center Selection by Promoting Adhesive Interactions between B Cells and Follicular Dendritic Cells.

Antibody affinity maturation, which is an antigen-based selection process for B cells, occurs in germinal centers (GCs). GCB cells must efficiently recognize, acquire, and present antigens from follicular dendritic cells (FDCs) to receive positive selection signals from T helper cells. Previous studies showed that GCB cells undergo adhesive interactions with FDCs, but the regulatory mechanisms underlying the cell adhesions and their functional relevance remain unclear.