The Role of Type-2 Conventional Dendritic Cells in the Regulation of Tumor Immunity

Abstract

Conventional dendritic cells (cDCs) orchestrate immune responses to cancer and comprise two major subsets: type-1 cDCs (cDC1s) and type-2 cDCs (cDC2s). Compared with cDC1s, which are dedicated to the activation of CD8+ T cells, cDC2s are ontogenically and functionally heterogeneous, with their main function being the presentation of exogenous antigens to CD4+ T cells for the initiation of T helper cell differentiation. cDC1s play an important role in tumor-specific immune responses through cross-presentation of tumor-derived antigens for the priming of CD8+ T cells, whereas little is known of the role of cDC2s in tumor immunity. Recent studies have indicated that human cDC2s can be divided into at least two subsets and have implicated these cells in both anti- and pro-tumoral immune responses. Furthermore, the efficacy of cDC2-based vaccines as well as cDC2-targeted therapeutics has been demonstrated in both mouse models and human patients. Here we summarize current knowledge about the role of cDC2s in tumor immunity and address whether these cells are beneficial in the context of antitumor immune responses.

Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors

“…The cDCs are tissue-resident DCs. The cDCs type 1 are specialized in activating CD8 + and type 2 on CD4 + T cells, both of which play a role in the regulation of anti-tumor immunity [ 75 , 76 ]. The place of their residency then further shapes their phenotype to form multiple subsets of these cells in peripheral tissues [ 77 ].…”

“…However, even though their role in anti-tumor immunity is necessary, it seems that it is insufficient and needs to be promoted by a cross-talk with other DC subtypes, namely the cDC2s [ 85 ]. The role of cDC2s in tumor immunity is ambivalent as these DCs can show either pro- or anti-tumorigenic activities [ 76 ]. Similar is true for mo-DCs and pDCs, both of which can adopt either pro- or anti-tumorigenic activities [ 86 , 87 ].…”

The soldiers needed to be awakened: Tumor-infiltrating immune cells

“…It was discovered that targeting XCR1 is crucial for the delivery of tumor antigen to cDC1 and, subsequently, CD8+T cell priming ( de Mingo Pulido et al, 2021 ). The cDC2-based vaccine may also potently inhibit tumor growth and prolong the survival ( Saito et al, 2022 ). Treatment with antibodies against the CD47-SIRPα axis could activate cDC2s, enhancing the cytotoxicity of CD8+ T cells ( Saito et al, 2022 ).…”

“…The cDC2-based vaccine may also potently inhibit tumor growth and prolong the survival ( Saito et al, 2022 ). Treatment with antibodies against the CD47-SIRPα axis could activate cDC2s, enhancing the cytotoxicity of CD8+ T cells ( Saito et al, 2022 ). FLT3 is a key factor for the differentiation and maturation of cDCs; thus, FLT3 agonist, CDX-301 (FLT3L), has been developed ( Kvedaraite and Ginhoux, 2022 ).…”

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

“… 25 , 34 cDC2s’ main function is considered to be the presentation of exogenous antigens (e.g., from extracellular pathogens) to different CD4 + T H subsets, although this subset is as functionally heterogeneous as it is ontogenetically. 35 , 36 In comparison to cDC1s, knowledge on cDC2s’ functions in anti-tumor responses is only starting to build up recently. It is emerging that cDC2s perform a non-redundant role in mobilizing both CD8 + T cell responses and CD4 + T H cell priming.…”