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:Abnormal Exacerbation of Moderately Differentiated Gastric Adenocarcinoma in a Patient with TAFRO Syndrome: An Impaired Tumor Immunity?
Abnormal Exacerbation of Moderately Differentiated Gastric Adenocarcinoma in a Patient with TAFRO Syndrome: An Impaired Tumor Immunity?
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TAFRO综合征是一种相对较新的疾病实体,于2010年首次报道。我们报告一例TAFRO综合征伴中分化胃腺癌异常加重的病例。TAFRO综合征的病理生理学在很大程度上尚不清楚,但由于该病通常对免疫抑制治疗有反应,并且由于据报道TAFRO综合征中滤泡辅助性T(Tfh)细胞急剧减少,可以推测涉及免疫系统失调。越来越多的证据表明,Tfh细胞通过支持异位淋巴结构在肿瘤免疫中发挥关键作用,这些结构是直接参与抗肿瘤活性的细胞(如CD8+ T细胞、NK细胞和巨噬细胞)的募集部位。事实上,据报道Tfh细胞与人类结直肠癌和乳腺癌的更长生存在正相关。结合我们对所报告患者中超进展性胃癌的观察,强烈提示TAFRO综合征中存在肿瘤免疫受损。
TAFRO syndrome is a relatively new disease entity first reported in 2010.
We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated.
Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8 + T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.
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