Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. Results: We identified 15 CD45+immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.1 and Prolif.2). Skin tumor progression reprogramed immune cells and led to a marked increase in the relative percentages of macrophages, cDC2, mDC, Tregs, and Neu. Macrophages, the largest cell cluster of immune cells in skin tumors. In addition, macrophages emerged as the predominant communication ‘hub’ in skin tumors, highlighting the importance of macrophages during skin tumor progression. In contrast, other immune cell clusters decreased during skin tumor progression, including DETC, γδT, ILC2, and LC. In addition, skin tumor progression dramatically upregulated Jak2/Stat3 expression and the interferon response across various immune cell clusters. Further, skin tumor progression activated T cells and NK cells indicated by elevated expression of IFN-γ and Granzyme B in skin tumors. Meanwhile, a pronounced infiltration of M2-macrophages and Tregs in skin tumors created an immunosuppressive microenvironment, consistent with the elevated expression of the Stat3 pathway in skin tumors. Conclusions: Our study elucidates the immune cell landscape of epidermal neoplasms, offering a comprehensive understanding of the immune response during skin tumor progression and providing new insights into cancer immune evasion mechanisms.
背景/目的：免疫细胞在肿瘤微环境中扮演着双重角色，既可抑制肿瘤形成，亦能促进肿瘤发生，从而决定肿瘤进展过程中的微环境功能。本研究旨在全面解析皮肤肿瘤进展过程中免疫细胞的应答特征。方法：通过单细胞RNA测序技术，我们在单细胞水平上对比分析了对照组小鼠皮肤与皮肤肿瘤组织中肿瘤微环境内的免疫细胞图谱。结果：我们鉴定出15个CD45+免疫细胞亚群，涵盖了功能特征明确的主要免疫细胞类型，包括巨噬细胞、朗格汉斯细胞（LC）、经典1型树突状细胞（cDC1）、经典2型树突状细胞（cDC2）、迁移/成熟树突状细胞（mDC）、表皮树突状T细胞（DETC）、真皮γδ T细胞（γδT）、T细胞、调节性T细胞（Tregs）、自然杀伤细胞（NK）、2型固有淋巴细胞（ILC2）、中性粒细胞（Neu）、肥大细胞（Mast）以及两个增殖性细胞群（Prolif.1与Prolif.2）。皮肤肿瘤进展重塑了免疫细胞组成，导致巨噬细胞、cDC2、mDC、Tregs和Neu的相对比例显著上升。巨噬细胞成为皮肤肿瘤中最大的免疫细胞群体，并在细胞间通讯网络中占据主导地位，凸显了其在皮肤肿瘤进展中的关键作用。与之相反，DETC、γδT、ILC2和LC等免疫细胞亚群在肿瘤进展过程中比例下降。此外，皮肤肿瘤进展显著上调了多种免疫细胞中Jak2/Stat3通路的表达及干扰素应答水平。同时，皮肤肿瘤中IFN-γ和颗粒酶B表达升高，提示T细胞与NK细胞处于激活状态。值得注意的是，皮肤肿瘤中M2型巨噬细胞与Tregs的显著浸润形成了免疫抑制微环境，这与肿瘤组织中Stat3通路表达上调的现象相一致。结论：本研究系统阐明了表皮肿瘤的免疫细胞图谱，深化了对皮肤肿瘤进展过程中免疫应答机制的理解，并为肿瘤免疫逃逸机制的研究提供了新的视角。
肿瘤(癌症)患者之家