CD27 costimulation supports metabolic fitness of CD4+ T cells by enhancing de novo nucleotide and protein synthesis.

T cells undergo many metabolic changes throughout the different phases of their response in lymphoid and nonlymphoid tissues. Cell metabolism meets demands for energy and biosynthesis, particularly during cell division and effector differentiation. As costimulatory receptors, CD28 and various TNF receptor (TNFR) family members shape T-cell clonal expansion, survival and effector functions and are important clinical targets.

CD4 T-cell help delivery to monocyte-derived dendritic cells promotes effector differentiation of helper and cytotoxic T cells.

Delivery of CD4 T-cell help optimizes CD8 T-cell effector and memory responses via CD40-mediated licensing of conventional dendritic cells (DCs). Using comparative vaccination settings that prime CD8 T cells in presence or absence of CD4 T-cell help, we observed that CD4 T-cell activation promoted influx of monocytes into the vaccine-draining lymph nodes (dLNs), where they differentiated into monocyte-derived (Mo)DCs, as defined by the most recent standards. Abrogation of these responses by CCR2-targeted depletion indicated that monocyte-derived cells in the dLN promoted T-helper 1 (Th1) type effector differentiation of CD4 T cells, as well as effector differentiation of CD8 T cells.

The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer.

Both type I interferon (IFN-I) and CD4 T-cell help are required to generate effective CD8 T-cell responses to cancer. We here outline based on existing literature how IFN-I signaling and CD4 T-cell help are connected. Both impact on the functional state of dendritic cells (DCs), particularly conventional (c)DC1.

PD-1 or CTLA-4 blockade promotes CD86-driven Treg responses upon radiotherapy of lymphocyte-depleted cancer in mice.

Radiotherapy (RT) is considered immunogenic, but clinical data demonstrating RT-induced T cell priming are scarce. Here, we show in a mouse tumor model representative of human lymphocyte-depleted cancer that RT enhanced spontaneous priming of thymus-derived (FOXP3+Helios+) Tregs by the tumor. These Tregs acquired an effector phenotype, populated the tumor, and impeded tumor control by a simultaneous, RT-induced CD8+ cytotoxic T cell (CTL) response.

Mechanism of action of PD-1 receptor/ligand targeted cancer immunotherapy.

Immunotherapy targeting the Programmed Death (PD-1) receptor/ligand (L) "checkpoint" rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co-treatments are required. To meet these demands, we must understand PD-1 function in detail.

Helpless Priming Sends CD8 T Cells on the Road to Exhaustion.

Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control.

CD4 T cell help creates memory CD8 T cells with innate and help-independent recall capacities.

CD4 T cell help is required for the generation of CD8 cytotoxic T lymphocyte (CTL) memory. Here, we use genome-wide analyses to show how CD4 T cell help delivered during priming promotes memory differentiation of CTLs. Help signals enhance IL-15-dependent maintenance of central memory T (T) cells.