Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York , USA.
J Invest Dermatol. 2012 Jun;132(6):1645-55. doi: 10.1038/jid.2012.34. Epub 2012 Mar 8.
Langerhans cells (LCs) are dendritic cells (DCs) localized to the epidermis. They should be the first antigen-presenting cells to encounter squamous cell carcinoma (SCC). The aim of this study was to investigate the ability of LCs isolated from human SCC to induce T-cell proliferation and polarization. We investigated the ability of LCs from SCC and peritumoral skin to induce T-cell proliferation and polarization. We also studied the effect of SCC supernatant on the ability of LCs from normal skin, in vitro-generated LCs, and DCs to activate and polarize T cells. LCs from SCC were stronger inducers of allogeneic CD4(+) and CD8(+) T-cell proliferation and IFN-γ production than LCs from peritumoral skin. We found that tumor supernatants (TSNs) were rich in immunosuppressive cytokines; despite this, allogeneic CD4(+) and CD8(+) T-cell proliferation and IFN-γ induction by LCs were augmented by TSN. Moreover, TSN facilitated IFN-γ induction by in vitro-generated LCs, but suppressed the ability of in vitro-generated DCs to expand allogeneic CD4(+) and CD8(+) T cells. We have demonstrated that LCs from SCC can induce type 1 immunity. TSN induces IFN-γ induction by in vitro-generated LCs. This contrasts greatly with prior studies showing that DCs from SCC cannot stimulate T cells. These data indicate that LCs may be superior to DCs for SCC immunotherapy and may provide a new rationale for harnessing LCs for the treatment of cancer patients.
郎格汉斯细胞（LCs）是定位于表皮的树突状细胞（DCs）。它们应该是首先遇到鳞状细胞癌（SCC）的抗原呈递细胞。本研究旨在研究从人 SCC 分离的 LCs 诱导 T 细胞增殖和极化的能力。我们研究了 SCC 和肿瘤周围皮肤的 LCs 诱导 T 细胞增殖和极化的能力。我们还研究了 SCC 上清液对正常皮肤、体外生成的 LCs 和 DCs 激活和极化 T 细胞能力的影响。与肿瘤周围皮肤的 LCs 相比，SCC 的 LCs 更能诱导同种异体 CD4(+)和 CD8(+)T 细胞增殖和 IFN-γ产生。我们发现肿瘤上清液（TSNs）富含免疫抑制细胞因子；尽管如此，TSN 仍增强了同种异体 CD4(+)和 CD8(+)T 细胞增殖和 IFN-γ诱导由 LCs 诱导。此外，TSN 促进了体外生成的 LCs 诱导 IFN-γ，但抑制了体外生成的 DCs 扩增同种异体 CD4(+)和 CD8(+)T 细胞的能力。我们已经证明 SCC 的 LCs 可以诱导 1 型免疫。TSN 诱导体外生成的 LCs 诱导 IFN-γ。这与先前的研究形成鲜明对比，先前的研究表明 SCC 的 DCs 不能刺激 T 细胞。这些数据表明 LCs 可能优于 SCC 免疫治疗中的 DCs，并为利用 LCs 治疗癌症患者提供了新的依据。
