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:CD169(+) sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.
CD169(+) sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.
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区域淋巴结中 CD169+ 巨噬细胞存在且 CD8+ TILs 丰富的结直肠癌提示更好的预后,应在免疫学上将其归类为与 dMMR 结直肠癌不同的抗肿瘤组。
错配修复缺陷/微卫星高度不稳定(dMMR/MSI-H)结直肠癌(CRC)患者无论肿瘤细胞PD-L1表达如何,均接受程序性死亡受体(PD)-1抗体治疗。我们既往发现,区域淋巴结(RLN)窦内CD169⁺巨噬细胞数量丰富与CRC中CD8⁺TIL(肿瘤浸润淋巴细胞)呈正相关,且与良好预后相关。然而,不同研究中dMMR/MSI-H CRC与CD8⁺ TIL或预后的关联并不一致。本研究尝试比较CRC中MMR状态、RLN内CD169⁺巨噬细胞、CD8⁺ TIL、PD-L1评分及预后之间的关系。方法与结果:对83例既往已进行MMR蛋白分析的手术切除CRC肿瘤进行免疫染色,发现其中9例为dMMR。RLN内CD169⁺巨噬细胞和CD8⁺ TIL数量与总生存期显著相关,而MMR状态无此相关性。根据MMR状态分组后,TIL标志物CD3、CD4、CD8和TIA-1阳性细胞,以及RLN内巨噬细胞标志物CD68和CD169阳性细胞的数量均无显著差异。此外,9例dMMR CRC中有5例检测了PD-L1表达,其综合阳性评分(CPS)均<1。我们发现,CRC的dMMR状态与RLN内CD169⁺巨噬细胞或CD8⁺ TIL数量无相关性。
RLN内存在CD169⁺巨噬细胞且CD8⁺ TIL丰富的CRC预后较好,应在免疫学上将其归为有别于dMMR CRC的另一种抗肿瘤类别。
AIMS: Mismatch-repair deficiency and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) is treated with programmed death (PD)-1 antibody regardless of PD-ligand (L)1 expression in tumor cells. We previously found that abundant CD169 + macrophages in regional lymph node (RLN) sinuses and CD8 + tumor-infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI-H CRC and CD8 + TILs or prognoses vary among studies. In this study, we attempted to compare the association between MMR status, CD169 + macrophages in RLNs, CD8 + TILs, PD-L1 scores, and prognoses in CRC. METHODS AND RESULTS: We immunostained 83 surgically resected CRC tumors that we previously analyzed for MMR proteins, and identified 9 that were dMMR. The number of CD169 + macrophages in RLNs and CD8 + TILs significantly correlated with overall survival, whereas MMR status did not. The number of cells positive for the TIL markers CD3, CD4, CD8, and TIA-1, and macrophage markers CD68 and CD169 in RLNs did not significantly differ between groups according to MMR status. Furthermore, combined positive scores (CPS) for PD-L1 expression in five of nine dMMR CRCs were all <1. We found that dMMR in CRC did not correlate with numbers of CD169 + macrophages in RLNs or CD8 + TILs. CONCLUSIONS: CRC with CD169 + macrophages in RLNs and abundant CD8 + TILs indicates a better prognosis and it should be immunologically classified as a different antitumor group from dMMR CRC.
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