Role of dendritic cell metabolic reprogramming in tumor immune evasion

Abstract

The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.

New Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases

“…In contrast, lipid accumulation such as cholesterol and oxysterol in DCs seems to inhibit DC migration, which may be associated with the activation of the PPARs and LXRα partially (Villablanca et al, 2010;Plebanek et al, 2020). Mice treated with resolvin E1, a lipid mediator derived from ω3 polyunsaturated fatty acids, exhibited a significantly reduced number of cutaneous migrated DCs in dLNs and suppressed T-cell induction and ear swelling response in the sensitization phase of contact hypersensitivity.…”

Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours

“…Conventional DC1 cells, which attract and promote cytotoxic and T H 1 cell responses, are associated with good prognosis, with enrichment of the cDC1 transcription profile being an indicator of patient survival in a range of cancers [ 187 , 190 ]. However, poor DC infiltration, incomplete differentiation, tolerogenic, or dysfunctional phenotypes limit the DCs’ ability to promote T cell activity [ 190 , 201 , 202 ].…”

A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids

“…The accumulation of lipid droplets (LDs) in tumour-associated DCs contributes to DC dysfunction by reducing antigen presentation and attenuating T cell activation (133)(134)(135)(136)(137). In addition to lipid storage in DCs, FAO was considered to have an active role in driving DCs towards a tolerogenic phenotype (138) possibly because the increased lipid storages in tumour-associated DCs can serve to fuel the FAO process by the stimulation of PPAR signalling (139). NK cells can be negatively affected by exogenous lipids, especially in the context of obesity (140)(141)(142).…”