Li Ran, Lin Ying, Wang Yu, Wang Shaoyuan, Yang Yang, Mu Xinlin, Chen Yusheng, Gao Zhancheng
Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.
The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China.
Front Oncol. 2021 Apr 1;11:620989. doi: 10.3389/fonc.2021.620989. eCollection 2021.
Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer. The tumor immune microenvironment (TIME) affects the anti-tumor immune response and the patient's prognosis, although the TIME in LUSC patients is incompletely understood.
We retrospectively collected surgical specimens from patients with previously untreated primary LUSC. Histopathological examination was used to identify tumor regions and adjacent regions, and imaging mass cytometry was used to characterize the immune cells in those regions. The results were compared between regions and between patients.
We identified heterogeneity in the TIME on comparing different patients with LUSC, although the tumor region and adjacent region both exhibited an immune response to the tumor. The TIME typically included a large number of infiltrating and activated T-cells, especially CD8 T-cells, which closely interacted with the tumor cells in the tumor region. There was limited infiltration of B-cells, NK cells, and NKT cells, while the major immune suppressor cells were CD33 myeloid-derived cells. We also identified a novel population of CD3CD4 cells with high expression of Foxp3 and TNFα, which might modulate the tumor microenvironment and play a proinflammatory role in the TIME.
The TIME of LUSC appears to be immunogenic and heterogenous, with predominant infiltration of activated CD8 T-cells. The interactions between the tumor cells and T-cells facilitate the anti-tumor activity. A novel subpopulation of CD3CD4 cells with high TNFα and Foxp3 expression may modulate the tumor microenvironment and play a proinflammatory role.
肺鳞状细胞癌（LUSC）是非小细胞肺癌的主要亚型。肿瘤免疫微环境（TIME）影响抗肿瘤免疫反应和患者预后，尽管LUSC患者的TIME尚未完全明确。
我们回顾性收集了先前未经治疗的原发性LUSC患者的手术标本。采用组织病理学检查确定肿瘤区域和相邻区域，并用成像质谱流式细胞术对这些区域的免疫细胞进行表征。对不同区域之间以及患者之间的结果进行比较。
比较不同LUSC患者时，我们发现TIME存在异质性，尽管肿瘤区域和相邻区域均对肿瘤表现出免疫反应。TIME通常包括大量浸润和活化的T细胞，尤其是CD8 T细胞，它们在肿瘤区域与肿瘤细胞密切相互作用。B细胞、NK细胞和NKT细胞的浸润有限，而主要的免疫抑制细胞是CD33髓系来源细胞。我们还鉴定出一群高表达Foxp3和TNFα的CD3CD4细胞，它们可能调节肿瘤微环境并在TIME中发挥促炎作用。
LUSC的TIME似乎具有免疫原性且异质性，以活化的CD8 T细胞为主浸润。肿瘤细胞与T细胞之间的相互作用促进了抗肿瘤活性。一种高表达TNFα和Foxp3的新型CD3CD4细胞亚群可能调节肿瘤微环境并发挥促炎作用。
