CD1d highly expressed on DCs reduces lung tumor burden by enhancing antitumor immunity.

ABSTRACT: Dendritic cells (DCs), as professional antigen?presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T?cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor?bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4+T and CD8+T cell activation, particularly cytotoxic T cells. All the T cells (NKT, CD4+T and CD8+T cells) upregulated CD69, CD107a and IFN?? after the adoptive transfer of CD1d?positive DCs (CD1d+DCs) and tumor growth was suppressed. With regard to the mechanism, we revealed that CD1d+DCs were concomitant with a higher expression of costimulatory molecules (CD40, CD80 and CD86) and MHCI/II, which are essential for DCs to present antigens to T cells. Consistently, CD1d+DCs displayed stronger activation?associated?ERK1/2 and NF??B signals; whereas JAK2?STAT3/6 signaling was required for maintaining a high level of CD1d on DCs. In lung cancer patients, the antitumor activities of all the T cells were enhanced with the increase of CD1d+DCs. Analysis of TCGA data revealed that high levels of CD1d indicated better outcomes for patients. Collectively, CD1d enhanced DC?based antitumor immunity, not only by targeting NKT, but also by activating CD4+T and CD8+T cells. CD1d+DCs may be superior to the bulk population of DCs in cancer immunotherapy.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6448128 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature