The differentiation of new human CD303+ Plasmacytoid dendritic cell subpopulations expressing CD205 and/or CD103 regulated by Non-Small-Cell lung cancer cells.

CD303+ plasmacytoid dendritic cells (pDCs) play an important role in the induction of immune tolerance and antitumor immunity. Here, we focused on the effect of NSCLC cells on the development of CD303+ pDC subsets expressing CD205 and/or CD103. The NSCLC cell line H1299 and primary NSCLC cells were incubated with DCs. The protein expression of costimulatory molecules on CD303+ pDCs, the production of pro-inflammatory and anti-inflammatory cytokines by CD303+ pDCs and the development of CD303+ pDC subsets were detected by using flow cytometry. Coculture with NSCLC cells modulates the protein expression of CD86 and HLA-DR on CD303+ pDCs. Moreover, NSCLC cells suppressed the production of IL-12 and IL-23 but facilitated the secretion of IL-27 and TGF-ß by CD303+ pDCs. There were new CD303+ pDC subsets expressing CD205 and/or CD103 in healthy donors and NSCLC patients: CD303+CD205+CD103+, CD303+CD205+CD103-, CD303+CD205-CD103+ and CD303+CD205-CD103- pDCs. NSCLC cells modulated the differentiation of CD303+ pDC subpopulations by regulating the protein expression of CD205 and/or CD103 on CD303+ pDCs. NSCLC cells may regulate the immune functions of CD303+ pDCs by modulating the expression of costimulatory molecules on DCs and the production of pro-inflammatory/anti-inflammatory cytokines by DCs. NSCLC cells also regulate the development of CD303+ pDC subsets expressing CD205 and/or CD103. These outcomes may reveal a new cellular mechanism leading to the NSCLC-induced immune-suppressive microenvironment.

Non-small Cell Lung Cancer Cells Modulate the Development of Human CD1c+ Conventional Dendritic Cell Subsets Mediated by CD103 and CD205.

Advanced non-small cell lung cancer (NSCLC) leads to a high death rate in patients and is a major threat to human health. NSCLC induces an immune suppressive microenvironment and escapes from immune surveillance in vivo. At present, the molecular mechanisms of NSCLC immunopathogenesis and the immune suppressive microenvironment induced by NSCLC have not been fully elucidated. Here, we focus on the effect of NSCLC cells on the development and differentiation of human CD1c+ conventional dendritic cell (DC) subsets mediated by CD205 and CD103. The peripheral blood mononuclear cells (PBMCs) were isolated from NSCLC patients and healthy donors. DCs were induced and cocultured with primary NSCLC cells or tumor cell line H1299. DCs without incubation with tumor cells are control. The protein expression of costimulatory molecules such as CD80 and CD86, HLA-DR, pro-/anti-inflammatory cytokines such as IL-10 and IL-12, and CD205 and CD103 on CD1c+ DCs was detected by flow cytometry. Our data revealed two new subpopulations of human CD1c+ DCs (CD1c+CD205+CD103+ and CD1c+CD205+CD103- DC) in healthy donors and NSCLC patients. NSCLC cells modulate the development of the CD1c+CD205+CD103+ DC and CD1c+CD205+CD103- DC subpopulations in vitro and ex vivo. NSCLC cells also suppress the expression of signal molecules such as CD40, CD80, CD86, and HLA-DR on CD1c+ DCs. In addition, the production of pro-inflammatory cytokines, including IL-12 and IL-23, is downregulated by NSCLC cells; however, the secretion of anti-inflammatory cytokines, such as IL-10 and IL-27, by CD1c+ DCs is upregulated by NSCLC cells. Our results suggest that NSCLC cells may induce immune tolerogenic DCs, which block DC-mediated anti-tumor immunity in NSCLC patients. Our data may be helpful in revealing new cellular mechanisms related to the induction of tolerogenic CD1c+ DCs by NSCLCs and the development of an immune suppressive microenvironment that causes tumor cells to escape immune surveillance. Our results indicate a potential role for CD1c+ DC subsets mediated by CD205 and CD103 in DC-mediated immunotherapy to target NSCLC in the future.