FIGURE 1. Phenotypic markers and pathways in mTEC development. The mTEC I subset is part of the mTEC^lo compartment and characterized by Ccl21 expression. mTEC II are the classically mature Aire+ mTEC^hi populations. mTEC III are the post-Aire terminally differentiated mTECs that also are found in the mTEC^lo compartment, and mTEC IV are the newly found tuftlike cells. Additionally, there has been a newly characterized proliferating TAC-TEC subset, and whether this subset is ( A ) progenitor of mTEC I and mTEC II ( 18 ) or ( B ) mTEC I leads to the TAC-TEC and mTEC II populations ( 24 ) requires further study. More

FIGURE 1. Signals regulating distinct epigenetic features of differentiating CD8 T cells. ( A ) As progenitor cells differentiate toward exhaustion, they alter their epigenome, becoming more accessible at effector genes (e.g., Ifng, Tbx21) and exhaustion genes (Tox, Eomes) while closing stemness genes (Tcf7, Bcl6, Id3). This is accomplished in part by changes in DNA methylation and histone modifications. Signals such as TCR stimulation, the balance of costimulation with inhibitory receptor signaling, cytokines, and metabolic signals in part drive these epigenetic changes. ( B ) Immunotherapeutic strategies that either limit the differentiation of progenitor to exhaustion or promote effector function in exhausted cells. Created by BioRender. More

FIGURE 1. Published Treg cell gene signatures and Foxp3 binding sites. ( A ) Number of genes in published Treg cell–specific gene sets, along with the year of publication (only from publications where the list or the number of differentially expressed genes was provided) ( 12 , 15–18 ). ( B ) Num... More

FIGURE 2. Putative mechanisms of Foxp3 function. ( A ) Direct displacement of TFs. Foxp3 competes with and displaces other TFs (e.g., Foxo1) at pre-existing regulatory elements (promoters, enhancers, or repressors) ( 10 ). ( B ) Direct recruitment of TFs. Foxp3 is poised at pre-existing regulatory elements in rTreg cells. During Treg cell activation, Foxp3 recruits the Polycomb complex to modify histones and repress gene expression ( 9 ). ( C ) Indirect regulation in trans. Foxp3 directly decreases expression of TCF1, resulting in indirect changes in gene expression ( 18 ). ( D ) Distal regulation at enhancer-promoter loops. Foxp3-bound sites engage in Treg cell–specific distal enhancer-promoter looping ( 53 ). ( E ) Cofactor-dependent regulation. Foxp3 is a member of different activating and repressive protein complexes ( 11 ). ( F ) Heterogeneous dimerization. Foxp3 can take different dimerization states with distinct motif binding preferences and functions ( 69 ). More

FIGURE 1. Multiomic profiling of T cells in PDAC can identify mechanisms of immunotherapy resistance. ( A ) T cells in PDAC are generally sparse, are exhausted, and have few neoantigenic targets for effective tumor cell killing. ( B ) Single-cell technologies can simultaneously reveal T cell pheno... More

FIGURE 2. Profiling cellular components of the PDAC TME through multiomics. ( A ) Specific cells within the PDAC TME, including MDSCs, TAMs, and CAFs, contribute to immunosuppression via signaling molecules and immune checkpoint expression. ( B ) Single-cell technologies can reveal novel cellular ... More

More

More

Mark M. Davis, Ph.D., Burt and Marion Avery Family Professor, Department of Microbiology and Immunology, and Director, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine; Investigator—Howard Hughes Medical Institute. More