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:Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients.
Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients.
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卵巢癌女性的治疗选择有限,免疫治疗对大部分患者效果不佳。肿瘤细胞从卵巢或输卵管扩散至腹腔,通常伴随大量腹水产生。腹水代表了一种独特的腹膜液体肿瘤微环境,其中存在肿瘤细胞和免疫细胞,包括细胞毒性淋巴细胞。我们对高级别浆液性卵巢癌患者腹水中的淋巴细胞进行了表征。我们的数据揭示了NK和CD8+ T淋巴细胞的存在,这些细胞表达CD103和CD49a,它们是组织驻留的标志物。此外,这些细胞高表达抑制性NKG2A受体,其中组织驻留NK细胞上的表达水平最高。具有这些特征的淋巴细胞也存在于原发肿瘤部位。功能实验表明,腹水中的组织驻留NK细胞对卵巢肿瘤细胞具有高度反应性。在体内小鼠模型中也观察到了类似结果,在该模型中,肿瘤生长时可在腹腔液中检测到组织驻留NK和CD8+T细胞。总之,我们的数据揭示了高度功能性的淋巴细胞群体的存在,这些细胞可能成为改善卵巢癌患者免疫治疗的靶点。
Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes.
We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer.
Our data reveal the presence of NK and CD8 + T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency.
Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8 + T cells were detected in the peritoneal fluid upon tumor growth.
Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
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