FOXP1 and KLF2 reciprocally regulate checkpoints of stem-like to effector transition in CAR T cells.

In cancer and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene networks. FOXP1, a hub in the stem-like network, promoted expansion and stemness of CAR T cells and limited excessive effector differentiation. In the effector network, KLF2 enhanced effector CD8+ T cell differentiation and prevented terminal exhaustion. Thus, we identified gene networks and hub transcription factors that controlled the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.

The Impact of Intraspecies and Interspecies Bacterial Interactions on Disease Outcome.

The human microbiota is an array of microorganisms known to interact with the host and other microbes. These interactions can be competitive, as microbes must adapt to host- and microorganism-related stressors, thus producing toxic molecules, or cooperative, whereby microbes survive by maintaining homeostasis with the host and host-associated microbial communities. As a result, these microbial interactions shape host health and can potentially result in disease. In this review, we discuss these varying interactions across microbial species, their positive and negative effects, the therapeutic potential of these interactions, and their implications on our knowledge of human well-being.