BTN2A1 targeting reprograms M2-like macrophages and TAMs via SYK and MAPK signaling.

Tumor-associated macrophages (TAMs), often adopting an immunosuppressive M2-like phenotype, correlate with unfavorable cancer outcomes. Our investigation unveiled elevated expression of the butyrophilin (BTN)2A1 in M2-like TAMs across diverse cancer types. We developed anti-BTN2A1 monoclonal antibodies (mAbs), and notably, one clone demonstrated a robust inhibitory effect on M2-like macrophage differentiation, inducing a shift toward an M1-like phenotype both in vitro and ex vivo in TAMs from patients with cancer.

Dendritic Cells Actively Limit Interleukin-10 Production Under Inflammatory Conditions DC-SCRIPT and Dual-Specificity Phosphatase 4.

Dendritic cell (DC)-based immunotherapy makes use of the DC's ability to direct the adaptive immune response toward activation or inhibition. DCs perform this immune orchestration in part by secretion of selected cytokines. The most potent anti-inflammatory cytokine interleukin-10 (IL-10) is under tight regulation, as it needs to be predominantly expressed during the resolution phase of the immune response.

DC-SCRIPT Regulates IL-10 Production in Human Dendritic Cells by Modulating NF-κBp65 Activation.

The balance between tolerance and immunity is important for the outcome of an infection or cancer, and dendritic cells (DCs) are key regulators of this balance. DC-specific transcript (DC-SCRIPT) is a protein expressed by DCs and has been demonstrated to suppress both TLR-mediated expression of IL-10 and glucocorticoid receptor-mediated transcription of glucocorticoid-induced leucine zipper (GILZ). Because GILZ is known to promote IL-10 production, we investigated whether these two processes are linked.

Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4+ T-cell responses.

Apoptotic cells represent an important source of self-antigens and their engulfment by dendritic cells (DCs) is usually considered to be related to tolerance induction. We report here an unexpectedly high level of human CD4(+) T-cell proliferation induced by autologous DCs loaded with autologous apoptotic cells, due to the activation of more than 10% of naive CD4(+) T cells. This proliferation is not due to an increase in the costimulatory capacity of DCs, but is dependent on apoptotic cell-associated material processed through an endo-lysosomal pathway and presented on DC MHC class II molecules.

Dendritic cells crosspresent antigens from live B16 cells more efficiently than from apoptotic cells and protect from melanoma in a therapeutic model.

Dendritic cells (DC) are able to elicit anti-tumoral CD8(+) T cell responses by cross-presenting exogenous antigens in association with major histocompatibility complex (MHC) class I molecules. Therefore they are crucial actors in cell-based cancer immunotherapy. Although apoptotic cells are usually considered to be the best source of antigens, live cells are also able to provide antigens for cross-presentation by DC.