Department of Experimental and Clinical Immunology, CAS Lamvac Biotech Co., Ltd., Guangzhou, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2019 Dec 10;10:2829. doi: 10.3389/fimmu.2019.02829. eCollection 2019.
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 . 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 (CD1cCD205CD103 and CD1cCD205CD103 DC) in healthy donors and NSCLC patients. NSCLC cells modulate the development of the CD1cCD205CD103 DC and CD1cCD205CD103 DC subpopulations and . 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.
晚期非小细胞肺癌（NSCLC）导致患者死亡率高，是对人类健康的重大威胁。NSCLC 诱导免疫抑制微环境并逃避免疫监视。目前，NSCLC 免疫发病机制的分子机制和 NSCLC 诱导的免疫抑制微环境尚未完全阐明。在这里，我们专注于 CD205 和 CD103 介导的 NSCLC 细胞对人类 CD1c 常规树突状细胞（DC）亚群发育和分化的影响。从 NSCLC 患者和健康供体中分离外周血单核细胞（PBMC）。诱导 DC 并与原发性 NSCLC 细胞或肿瘤细胞系 H1299 共培养。未与肿瘤细胞孵育的 DC 作为对照。通过流式细胞术检测 CD1c DC 上共刺激分子（如 CD80 和 CD86、HLA-DR）、前/抗炎细胞因子（如 IL-10 和 IL-12）以及 CD205 和 CD103 的蛋白表达。我们的数据揭示了健康供体和 NSCLC 患者中两种新的人类 CD1c DC 亚群（CD1cCD205CD103 和 CD1cCD205CD103 DC）。NSCLC 细胞调节 CD1cCD205CD103 DC 和 CD1cCD205CD103 DC 亚群的发育，并抑制 CD1c DC 上信号分子（如 CD40、CD80、CD86 和 HLA-DR）的表达。此外，NSCLC 细胞下调包括 IL-12 和 IL-23 在内的促炎细胞因子的产生，而 NSCLC 细胞上调 CD1c DC 的抗炎细胞因子（如 IL-10 和 IL-27）的分泌。我们的结果表明，NSCLC 细胞可能诱导免疫耐受的 DC，从而阻断 NSCLC 患者中 DC 介导的抗肿瘤免疫。我们的数据可能有助于揭示与 NSCLC 诱导耐受 CD1c DC 相关的新细胞机制，并阐明导致肿瘤细胞逃避免疫监视的免疫抑制微环境。我们的结果表明，CD205 和 CD103 介导的 CD1c DC 亚群在未来针对 NSCLC 的 DC 介导免疫治疗中可能具有潜在作用。
