The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity

Abstract

Dendritic cells (DCs) are key orchestrators of immune responses. A specific DC subset, conventional type 1 DCs (cDC1s), has been recently associated with human cancer patient survival and, in preclinical models, is critical for the spontaneous rejection of immunogenic cancers and for the success of T cell–based immunotherapies. The unique role of cDC1 reflects the ability to initiate de novo T cell responses after migrating to tumor-draining lymph nodes, as well as to attract T cells, secrete cytokines, and present tumor antigens within the tumor microenvironment, enhancing local cytotoxic T cell function. Strategies aimed at increasing cDC1 abundance in tumors and enhancing their functionality provide attractive new avenues to boost anti-tumor immunity and overcome resistance to cancer immunotherapies.

2’3’-cGAMP is an immunotransmitter produced by cancer cells and regulated by ENPP1

“…We established E0771 orthotopic tumors in mice, followed by intratumoral injection of neutralizing STING to deplete extracellular cGAMP, and excision of the tumors to stain for tumor-associated leukocytes. In WT E0771 tumors, compared to non-binding STING, neutralizing STING significantly decreased the CD11c + (dendritic cell or DC) population and the CD103 + CD11c + (conventional type I dendritic cell or cDC1) population 35 in the CD45 + MHC II + (tumor-associated antigen presenting cell or APC) population, suggesting that extracellular cGAMP can be detected by the immune system ( Fig. 4f and Extended Data Fig.…”

A functional variant near XCL1 gene improves breast cancer survival via promoting cancer immunity

“…We identified the importance of the A allele of rs1024176, which leads to higher XCL1 expression. Of interest, XCL1 is produced and secreted by intratumoral NK cells and then activates CD8 + T cells to attack tumors . To achieve this, conventional DC1s are attracted to the tumor microenvironment, where they present tumor antigens, migrate into tumor‐draining lymph nodes to activate CD8 + T cells and trigger antitumor immunity to enhance patient survival.…”

“…32 Similar to other antigen-presenting cells, DC1s present exogenous and endogenous antigens to cytotoxic T cells and trigger their effector functions in the tumor microenvironment, which is thought to thus prime immunotherapy in human cancers. 30,35 Because DC1s are very rare in tumors, they have not been investigated in humans in as much detail as they have been in mice. 36 Therefore, recent studies have developed a gene expression signature to represent the level of DC1s.…”

“…Of interest, XCL1 is produced and secreted by intratumoral NK cells and then activates CD8 + T cells to attack tumors. 30 To achieve this, conventional DC1s are attracted to the tumor microenvironment, where they present tumor antigens, migrate into tumordraining lymph nodes to activate CD8 + T cells and trigger antitumor immunity to enhance patient survival. To examine whether DC1s have infiltrated tumor tissues, recent studies have used the expression of a set of genes as a DC1 signature to indicate DC1 accumulation in human tissue.…”

Functional Impairment of Circulating FcεRI+ Monocytes and Myeloid Dendritic Cells in Hepatocellular Carcinoma and Cholangiocarcinoma Patients

“…However, in vitro propagated DCs from HCC patients display a decreased ability to produce IL-12 (4), HCC tumor-derived alpha-fetoprotein impairs both the differentiation and T-cell stimulatory activity of human DCs (5). In the same line, tumor immune evasion is associated with the defective DC function in cancer patients as a result of decreased numbers of competent DCs and accumulation of immature cells (6,7).…”