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:Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern.
Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern.
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结直肠癌肝转移(CRC-LM)可呈现不同组织学生长模式(HGP),从而影响免疫细胞与肿瘤细胞间的相互作用。本研究采用多光谱数字病理学,在HGP背景下探究CRC-LM中淋巴细胞浸润的空间分布。促结缔组织增生型(dHGP)和非促结缔组织增生型(ndHGP)转移灶中央区域的免疫细胞密度无统计学显著差异。空间分析显示,dHGP转移灶周边区域CD8阳性和CD20阳性细胞浸润较高;ndHGP转移灶中CD4阳性和CD45RO阳性细胞浸润较多。
不过,ndHGP转移灶浸润边缘(IM)的反应性间质区CD4阳性、CD20阳性和CD45RO阳性细胞密度更高。以CD8/CD4比值评估TIL浸润的抗肿瘤状态时,包裹型转移灶浸润边缘向肿瘤中心延伸至400微米范围内的比值较高(P<0.05)。
值得注意的是,dHGP转移灶浸润边缘上皮区CD8阳性细胞浸润更高,表现为CD8上皮/CD8间质比值增加,提示包裹型病灶存在抗肿瘤活性。
总的来说,两种HGP转移灶浸润边缘的CD8阳性细胞总量相近;然而,在dHGP转移灶中,一些细胞毒性细胞能够进入肿瘤巢,而在ndHGP转移灶中则仍被限制于间质区域。
Colorectal cancer liver metastases (CRC-LM) present differential histologic growth patterns (HGP) that determine the interaction between immune and tumor cells.
We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the HGP using multispectral digital pathology.
We did not find statistically significant differences of immune cell densities in the central regions of desmoplastic ( d HGP) and non-desmoplastic ( nd HGP) metastases. The spatial evaluation reported that d HGP-metastases displayed higher infiltration by CD8 + and CD20 + cells in peripheral regions as well as CD4 + and CD45RO + cells in nd HGP-metastases.
However, the reactive stroma regions at the invasive margin (IM) of nd HGP-metastases displayed higher density of CD4 + , CD20 + , and CD45RO + cells. The antitumor status of the TIL infiltrates measured as CD8/CD4 reported higher values in the IM of encapsulated metastases up to 400 m towards the tumor center ( p < 0. 05).
Remarkably, the IM of d HGP-metastases was characterized by higher infiltration of CD8 + cells in the epithelial compartment parameter assessed with the ratio CD8 epithelial /CD8 stromal , suggesting anti-tumoral activity in the encapsulating lesions. Taking together, the amount of CD8 + cells is comparable in the IM of both HGP metastases types.
However, in d HGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in nd HGP-metastases.
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