Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I

Abstract

Tumors can induce generation and accumulation of the immunosuppressive cells such as regulatory T cells in the tumor

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

“…For instance, murine lung cancer could "educate" cDCs to differentiate into CD11c low CD11b high Ia low regDCs that inhibit T cell response, as was reported by Liu et al using the freshly isolated tumor cells to mimic the tumor microenvironment in DC co-culture studies [13]. Norian [14].…”

“…Plasmacytoid regDCs might express CCR9 [26]; in cancer, plasmacytoid regDCs may be identified as cells expressing FOXO3 [27]. In addition, tumor-induced regDCs have been described as DCs expressing low levels of CD11c, MHC class II and co-stimulatory CD80 and CD86 molecules and high levels of CD11b [13,19]. Overall, both phenotypic and functional characteristics of reported regDC subsets are markedly different in various experimental conditions and model systems, suggestion not only the plasticity of their differentiation and dependence on the local microenvironment, but potentially the different origin of functionally immunosuppressive or tolerogenic regDCs.…”

“…Tumor UPR-treated DCs upregulated expression of arginase and pro-inflammatory tumorigenic cytokines; they also downregulated cross-presentation of antigen, fail to effectively cross-prime CD8 + T cells causing T cell activation without proliferation and dominantly suppress crosspriming by bystander DCs [64], suggesting the appearance of regulatory phenotype. In another study, using the freshly isolated tumor cells to mimic the tumor microenvironment, the authors found that tumor cells could drive DCs to differentiate into regDCs with a CD11c low CD11b high Ia low phenotype and high expression of IL-10, NO, vascular endothelial growth factor (VEGF) and arginase I [13]. Tumor-derived PgE2 was the main inducer of arginase I in regDCs and arginase I played the major role in suppressing CD4+ T cell response by regDCs [13].…”

Intratumoral dendritic cells in the anti-tumor immune response

“…Regulatory DCs in the tumor microenvironment and systemic organs have been identified to mediate suppression of T-cell responses against tumors. 9,10 By contrast, marginating DCs of the tumor microenvironment can cross-present tumor antigens and stably engage tumor-specific T cells. 12 Moreover, DCs in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and promote a protective immune response mediated by T cells against cancer.…”

Tolerogenic dendritic cells and their applications in transplantation

“…Mouse CD11b high Ia low DCregs induced by 3LL lung cancer could suppress T-cell responses through arginase I. 37 The pDCs, which are differentiated from lymphoid progenitor cells in lymphoid organs, have been found to be able to regulate T-cell responses to alloantigens and prolong organ graft survival. 38,39 These regulatory pDCs exhibit a semimature phenotype and are more likely than imDCs to induce the generation of Tregs, Meanwhile, pDCs change much less than imDCs in vivo after exposure to an inflammatory microenvironment.…”