CD8+ T Cells Form the Predominant Subset of NKG2A+ Cells in Human Lung Cancer
CD8+ T Cells Form the Predominant Subset of NKG2A+ Cells in Human Lung Cancer
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DOI：
10.3389/fimmu.2019.03002
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发表时间：
2020-01-17
影响因子：
7.3
通讯作者：
Chai, Ying
中科院分区：
文献类型：
--
作者：
Chen, Yongyuan;Xin, Zhongwei;Chai, Ying
背景：NKG2A是T细胞和自然杀伤细胞（NK）的抑制受体。持续激活促进T细胞和NK细胞表达NKG2A，导致慢性感染和癌症的进展。然而，NKG2A（+）淋巴细胞在人肺癌中的特征和亚群尚不清楚。方法：利用肿瘤免疫估计资源数据库和配对生物标本的免疫图谱，揭示人类癌症中NKG2A表达与免疫浸润水平的相关性，以及人类肺癌中NKG2A（+）淋巴细胞的特征。结果：我们通过肿瘤免疫估计资源数据库发现，在34种人类癌症中，KLRC1表达与CD8(+) t细胞浸润水平尤其相关。此外，NKG2A(+) CD8(+) T细胞是NKG2A（+）淋巴细胞在人肺癌中的主要亚群。与配对的正常肺组织相比，肿瘤组织中NKG2A(+) NK细胞减少。肿瘤浸润性NKG2A(+) CD8(+) T细胞表达组织常驻记忆T细胞（T- rm细胞）和耗竭T细胞标记物。肿瘤浸润的NKG2A(+) CD8(+) T细胞分泌的细胞因子和细胞毒分子明显低于NKG2A(-) CD8(+) T细胞。在T细胞受体激活剂的刺激下，肿瘤浸润性NKG2A(+) CD8(+) T细胞可以分泌大量颗粒酶b。结论：我们的研究结果表明，肿瘤浸润性NKG2A(+) CD8(+) T细胞形成了人类肺癌NKG2A（+）细胞的主要亚群，并提示靶向NKG2A(+) CD8(+) T细胞是未来抗肺癌免疫治疗的一种有希望的方法。
Background: NKG2A is an inhibitory receptor of both T cells and natural killer (NK) cells. Persistent activation promotes T cells and NK cells to express NKG2A and results in the progression of chronic infection and cancer. However, the characteristics and subsets of NKG2A(+) lymphocytes in human lung cancer are still unclear. Methods: Here, we used the Tumor Immune Estimation Resource database and immune profiling of paired biospecimens to uncover the correlation between NKG2A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A(+) lymphocytes in human lung cancer. Results: We found that KLRC1 expression was especially correlated with CD8(+) T-cell infiltration levels in 34 types of human cancer through the Tumor Immune Estimation Resource database. Moreover, NKG2A(+) CD8(+) T cells were the predominant subset of NKG2A(+) lymphocytes in human lung cancer. In contrast, the NKG2A(+) NK cells were decreased in tumors compared with the paired normal lung tissue. Tumor-infiltrating NKG2A(+) CD8(+) T cells expressed tissue-resident memory T cell (T-RM cell) and exhausted T-cell markers. Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A(+) CD8(+) T cells were significantly lower than those secreted by NKG2A(-) CD8(+) T cells in vitro. When stimulated with T-cell receptor activator, tumor-infiltrating NKG2A(+) CD8(+) T cells could secrete large amounts of granzyme B. Conclusions: Our findings demonstrate that tumor-infiltrating NKG2A(+) CD8(+) T cells form the predominant subset of NKG2A(+) cells in human lung cancer and suggest that targeting NKG2A(+) CD8(+) T cells is a promising approach for future anti-lung cancer immunotherapy.