RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8(+) T cells towards the center of human lung tumors.
Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8(+) T cells towards the center of human lung tumors.
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肺癌是全球癌症相关死亡的主要原因。尽管近年来组织免疫学取得了进展,但人们对肺肿瘤中组织驻留淋巴细胞亚群的空间分布知之甚少。利用高参数流式细胞术,我们鉴定出组织驻留淋巴细胞,包括组织驻留NK(trNK)细胞和CD8+组织驻留记忆T(TRM)细胞,在人非小细胞肺癌(NSCLC)中向肿瘤中心积聚。趋化因子受体表达模式表明,trNK细胞与CD8+ TRM细胞具有不同的肿瘤浸润和/或驻留模式。与CD8+ TRM细胞相比,trNK细胞和ILC通常表达低水平的免疫检查点受体,且与肿瘤中的位置无关。
此外,trNK细胞和CD8+ TRM细胞中颗粒酶的表达在肿瘤中心最高,且肿瘤内CD49a+CD16- NK细胞具有功能,对靶细胞刺激的应答强于其CD49a-对应细胞,表明trNK细胞在肺肿瘤中具有功能相关性。
总之,本研究对人NSCLC中淋巴细胞亚群的空间定位为组织驻留免疫细胞的组成和功能提供了新的见解,提示trNK细胞和CD8+ TRM细胞在肺肿瘤中的作用及其对未来治疗策略的潜在意义。
Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little is known about the spatial distribution of tissue-resident lymphocyte subsets in lung tumors. Using high-parameter flow cytometry, we identified an accumulation of tissue-resident lymphocytes including tissue-resident NK (trNK) cells and CD8 + tissue-resident memory T (T RM ) cells toward the center of human non-small cell lung carcinomas (NSCLC).
Chemokine receptor expression patterns indicated different modes of tumor-infiltration and/or residency between trNK cells and CD8 + T RM cells. In contrast to CD8 + T RM cells, trNK cells and ILCs generally expressed low levels of immune checkpoint receptors independent of location in the tumor.
Additionally, granzyme expression in trNK cells and CD8 + T RM cells was highest in the tumor center, and intratumoral CD49a + CD16 - NK cells were functional and responded stronger to target cell stimulation than their CD49a - counterparts, indicating functional relevance of trNK cells in lung tumors.
In summary, the present spatial mapping of lymphocyte subsets in human NSCLC provides novel insights into the composition and functionality of tissue-resident immune cells, suggesting a role for trNK cells and CD8 + T RM cells in lung tumors and their potential relevance for future therapeutic approaches.
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