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:Finding the right help in the tumor microenvironment.
Finding the right help in the tumor microenvironment.
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TIL(肿瘤浸润淋巴细胞)(TILs)包含大量介导促肿瘤和抗肿瘤功能的CD4+ T细胞。虽然CD4+ Tregs已被充分表征并已知促进肿瘤免疫逃逸,但识别肿瘤抗原并限制疾病进展的CD4+ Th细胞的特征仍未被充分区分。在本期JCI中,Duhen等人分析了头颈部鳞状细胞癌或结肠癌患者的肿瘤,并鉴定出一个独特的程序性细胞死亡1阳性、ICOS1阳性(PD-1+ICOS1+)CD4+ TILs亚群,该亚群高度富集识别肿瘤相关抗原的能力。这些细胞定位于肿瘤内MHC II+抗原呈递细胞和CD8+ T细胞附近,在那里它们似乎增殖并几乎完全作为Th细胞发挥作用。这些潜在治疗性Th细胞可用于监测患者预后,并有望在开发个性化过继细胞和疫苗为基础的免疫治疗方法以改善患者预后方面具有重要效用。
Tumor-infiltrating lymphocytes (TILs) contain substantial numbers of CD4+ T cells mediating pro- and antitumor functions. While CD4+ Tregs are well characterized and known to promote tumor immune evasion, the fingerprint of CD4+ Th cells that recognizes tumor antigens and serves to restrict disease progression has remained poorly discriminated. In this issue of the JCI, Duhen et al. analyzed tumors from patients with head and neck squamous cell carcinoma or colon carcinoma and identified a unique programmed cell death 1-positive, ICOS1-positive (PD-1+ICOS1+) subpopulation of CD4+ TILs highly enriched for the ability to recognize tumor-associated antigens.
These cells localized proximally to MHC II+ antigen-presenting cells and CD8+ T cells within tumors, where they appeared to proliferate and function almost exclusively as Th cells. These potentially therapeutic Th cells can be monitored for patient prognosis and are expected to have substantial utility in developing personalized adoptive cell- and vaccine-based immunotherapeutic approaches for improving patient outcomes.
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