Broadening immune responses through antigen spreading remains the 'Holy Grail' of cancer immunotherapy. A study by Ma and colleagues reveals that vaccine boosting of chimeric antigen receptor (CAR)-T cells in mice promotes endogenous immunity and elicits antigen spread to eliminate antigenically heterogenous solid tumors through a mechanism crucially dependent on interferon (IFN)γ.

The DNA double-strand break (DSB) repair factor 53BP1 has long been implicated in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, the dissection of the underlying molecular activities is hampered by a paucity of studies [V(D)J] and plurality of phenotypes (CSR) associated with 53BP1 deficiency. Here, we revisit the currently accepted roles of 53BP1 in antibody diversification in view of the recent identification of its downstream effectors in DSB protection and latest advances in genome architecture. We propose that, in addition to end protection, 53BP1-mediated end-tethering stabilization is essential for CSR. Furthermore, we support a pre-DSB role during V(D)J recombination. Our perspective underscores the importance of evaluating repair of DSBs in relation to their dynamic architectural contexts.

RNA is integral to the regulatory circuits that control cell identity and behavior. Cis-regulatory elements in mRNAs interact with RNA-binding proteins (RBPs) that can alter RNA sequence, stability, and translation into protein. Similarly, long noncoding RNAs (lncRNAs) scaffold ribonucleoprotein complexes that mediate transcriptional and post-transcriptional regulation of gene expression. Indeed, cell programming is fundamental to multicellular life and, in this era of cellular therapies, it is of particular interest in T cells. Here, we review key concepts and recent advances in our understanding of the RNA circuits and RBPs that govern mammalian T cell differentiation and immune function.

Celiac disease (CeD) is an immune disorder characterized by gluten intolerance that can be unleashed by enteric viral infections in mice. However, Sanchez-Medina et al. recently identified a murine commensal protist, Tritrichomonas arnold, that protects against reovirus-induced intolerance to dietary protein by counteracting virus-induced epithelial stress and proinflammatory dendritic cell (DC) activation.