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:Tumor-infiltrating plasma cells are a prognostic factor in penile squamous cell carcinoma.
Tumor-infiltrating plasma cells are a prognostic factor in penile squamous cell carcinoma.
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阴茎癌(PeCa)是一种罕见疾病,转移阶段预后较差。目前既无有效的辅助治疗,也无姑息治疗选择。该领域的研究迄今未能建立可靠的生存预测指标。为识别PeCa的预后靶点,本项目聚焦于表征肿瘤微环境(TME)。研究纳入93例PeCa男性患者队列,用于构建组织芯片并进行CD3、CD4、CD8、CD20、CD56、CD138、FoxP3和PD-L1的免疫组化染色。使用数字图像分析评估肿瘤浸润免疫细胞的数量和空间分布。肿瘤细胞和免疫细胞的PD-L1染色采用人工评分(联合阳性评分(CPS))。T细胞、T辅助细胞、细胞毒性T细胞(CTL)和调节性T细胞在>90%的PeCa中检出,B细胞在88%中检出,浆细胞在85%中检出,NK细胞在23%中检出。约50%的PeCa样本为PD-L1阳性。在单因素生存分析中,高PD-L1 CPS、浆细胞、CTL和B细胞与有利的总生存期(OS)显著相关,后两者与不良的无复发生存期相关。在多因素分析中,浆细胞仍是有利OS的显著因素(p = 0.04)。
在本研究中,与其他已确定的PeCa预后因素相比,TME中的免疫细胞,尤其是浆细胞,与患者生存呈有利相关。同时,浆细胞已被讨论与促进对现代免疫治疗的应答有关。本研究结果支持这一观点。
Penile cancer (PeCa) is a rare disease with poor prognosis in the metastatic stage. Neither effective adjuvant nor palliative therapeutic options are available. Research efforts in this field have so far failed to establish robust predictors of survival. To identify prognostic targets in PeCa, the current project focused on characterizing the tumor microenvironment (TME). A study cohort of 93 men with PeCa was used for the construction of a tissue microarray and immunohistochemical staining for CD3, CD4, CD8, CD20, CD56, CD138, FoxP3, and PD-L1. The quantity and spatial distribution of tumor-infiltrating immune cells were analyzed using digital image analysis. PD-L1 staining of tumor and immune cells was manually scored (combined positivity score (CPS)).
T cells, T helper cells, cytotoxic T cells (CTLs), and regulatory T cells were detected in > 90% of PeCa and B cells in 88%, plasma cells in 85%, and NK cells in 23%. Approximately 50% of the PeCa samples were PD-L1 positive. In the univariate survival analysis, high PD-L1 CPS, plasma cells, CTLs, and B cells were significantly associated with favorable overall survival (OS), and the latter two with adverse recurrence-free survival.
In multivariate analysis, plasma cells remained a significant factor for favorable OS (p = 0. 04). In this study, the immune cells in the TME, especially plasma cells, were favorably associated with patient survival compared to other established prognostic factors in PeCa. Contemporarily, plasma cells have been discussed in the light of contributing to responses to modern immunotherapies. The results of this study support this notion.
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