Dendritic Cell Metabolism and Function in Tumors

Tumors can disrupt normal DC functions to evade immune control. Adverse conditions and factors in the tumor milieu modulate specific transcriptional programs and metabolic processes in infiltrating DCs to inhibit their immunogenic activity. Cancer-associated DCs with altered mitochondrial and lipid metabolism demonstrate reduced capacity to elicit T cell-based responses against tumors. Targeting metabolic pathways in intratumoral DCs might be used to elicit durable anticancer immunity and enhance the efficacy of T cell-based immunotherapies. Dendritic cells (DCs) are fundamental for the initiation and maintenance of immune responses against malignant cells. Despite the unique potential of DCs to elicit robust anticancer immunity, the tumor microenvironment poses a variety of challenges that hinder competent DC function and consequently inhibit the development of protective immune responses. Here, we discuss recent studies uncovering new molecular pathways and metabolic programs that tumors manipulate in DCs to disturb their homeostasis and evade immune control. We also examine certain state-of-the-art strategies that seek to improve DC function and elicit antitumor responses in hosts with cancer. Understanding and modulating DC metabolism and activity within tumors might help improve the efficacy of T cell-centric immunotherapies. Dendritic cells (DCs) are fundamental for the initiation and maintenance of immune responses against malignant cells. Despite the unique potential of DCs to elicit robust anticancer immunity, the tumor microenvironment poses a variety of challenges that hinder competent DC function and consequently inhibit the development of protective immune responses. Here, we discuss recent studies uncovering new molecular pathways and metabolic programs that tumors manipulate in DCs to disturb their homeostasis and evade immune control. We also examine certain state-of-the-art strategies that seek to improve DC function and elicit antitumor responses in hosts with cancer. Understanding and modulating DC metabolism and activity within tumors might help improve the efficacy of T cell-centric immunotherapies. host-derived molecules that can initiate and drive a noninfectious inflammatory response. cellular state induced by the perturbation of ER homeostasis, characterized by accumulation of misfolded proteins in this organelle. epithelial cells acquire a mesenchymal-like phenotype, a process that is accompanied by the loss of cell adhesion properties and augmented mobility. 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate, inhibitor of carnitine palmitoyltransferase (CPT1), an enzyme necessary for FAO in mitochondria. beta-oxidation; the breakdown of fatty acids to generate acetyl-CoA that is incorporated into the TCA. multienzyme complex driving cellular lipogenesis. group of genes encoding cell surface proteins mediating the recognition of self and non-self by the immune system. catalytic subunit of two protein complexes (mTORC1 and mTORC2) that are major regulators of cell growth, proliferation, and metabolism. changes in mitochondrial morphology that promote or inhibit mitochondrial function according to the functional and metabolic status of cells. Mitochondrial fusion promotes ETC organization that enhances FAO and efficient oxphos. Mitochondrial fission generates fragmented mitochondria unable to perform oxphos, favoring glycolytic metabolism. use of enzymes to oxidize carbon sources in order to synthesize ATP via the electron transport chain in mitochondria during aerobic respiration. molecules derived from an infectious non-self-entity, which stimulate an inflammatory response. germline-encoded proteins that sense invading pathogens or endogenous damage signals to initiate and regulate immune responses. regulator of FA storage and glucose metabolism; nuclear receptor whose activation drives the expression of genes involved in FAO. T cells with the ability to regulate immune responses by the secretion of cytokines (e.g., IL-10 and TGF-β) or by expressing regulatory ligands (CTL-4); generally defined by the expression of Forkhead box protein P3. capacity of cells to self-renew and maintain the potential to differentiate into distinct cell populations. In cancer, stemness can be related to malignancy, metastasis, and drug resistance. phenotype characterized by the activation of immunosuppressive mechanisms. In DCs, it is defined by low expression of MHC and co-stimulatory molecules and cytokines, lack of antigen-presenting capacity and the induction of Tregs. molecular, cellular, and extracellular milieu generated by malignant solid masses. molecular adaptive cellular mechanism triggered in response to the accummulation of misfolded or unfolded proteins in the ER.