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.
肿瘤细胞治疗研究
英文原题:Profiling of rare immune cell populations and integrative analysis identify immune ecotypes in newly diagnosed meningiomas.
Profiling of rare immune cell populations and integrative analysis identify immune ecotypes in newly diagnosed meningiomas.
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脑膜瘤(MGMs)是成人中最常见的原发性颅内肿瘤,其中相当一部分表现出侵袭性临床行为。免疫治疗是一种潜在的替代治疗选择,尽管 MGMs 传统上被认为是免疫冷肿瘤。
本研究探讨了特征描述较少的免疫细胞亚群 B 细胞、自然杀伤(NK)细胞和粒细胞,及其与主要免疫细胞群的关联和预后意义。为此,我们在一个临床注释完善的多中心队列中进行了组织细胞术分析,该队列包含 97 例新诊断的 MGMs,涵盖所有 WHO 级别(1、2、3 级)和 DNA 甲基化类别(良性、中间型、恶性)。将所得浸润数据与既往发表的关于肿瘤相关巨噬细胞(TAMs)和肿瘤浸润 T 淋巴细胞(TILs)的数据整合,以识别 MGM 免疫生态型。
总体而言,B 细胞、NK 细胞、中性粒细胞和嗜酸性粒细胞的浸润率显示频率较低,且在不同肿瘤间差异很大。值得注意的是,我们在伴有染色体臂 10q 和 22q 缺失的 MGM 中观察到 B 细胞数量显著降低,而在伴有染色体臂 1p 缺失的患者中发现 T 细胞数量较低。
此外,NK 细胞和嗜酸性粒细胞在 1 级和良性肿瘤中富集,而中性粒细胞在恶性病例中占优势。尽管其丰度相对较低,但中性粒细胞频率升高被证明是生存不良的独立预后因素。
重要的是,随后整合来自同一患者队列的 TAM 和 TIL 数据,揭示了五种不同的免疫生态型,每种均显示出特征性的免疫细胞浸润模式和有差异的生存结局。
总之,本研究提供了MGM中各种罕见免疫细胞亚型的扩展概述,并证明了它们整合到不同的预后免疫生态型中,从而能够在未来的临床研究中进行更好的分层。
Meningiomas (MGMs) are the most common primary intracranial tumors in adults with a substantial subset exhibiting aggressive clinical behavior. Immunotherapy represents a potential alternative treatment option, even though MGMs have traditionally been considered immunologically cold tumors.
This study explored less characterized immune cell subsets B cells, natural killer (NK) cells, and granulocytes and their associations with major immune cell populations as well as their prognostic implications.
For this purpose, we performed tissue cytometry analysis in a clinically well-annotated multi-center cohort of 97 newly diagnosed MGMs encompassing all WHO grades (1, 2, 3) and DNA methylation classes (benign, intermediate, malignant). Resulting infiltration data were integrated with previously published data on tumor-associated macrophages (TAMs) and tumor-infiltrating T lymphocytes (TILs) to identify MGM immune ecotypes.
Overall, infiltration rates of B cells, NK cells, neutrophils, and eosinophils showed lower frequencies and varied widely across tumors.
Notably, we observed significantly lower numbers of B cells in MGM with losses in chromosomal arms 10q and 22q, while lower number of T cells were found in patients with a loss of chromosomal arm 1p.
In addition, NK cells and eosinophils were enriched in grade 1 and benign tumors, whereas neutrophils predominated in malignant cases. Despite their relatively low abundance, elevated neutrophil frequencies turned out to be an independent of prognostic factor for poor survival.
Importantly, subsequent integration of TAM and TIL data derived from the same patient cohort unraveled five distinct immune ecotypes, each displaying characteristic immune cell infiltration patterns and differential survival outcomes. Altogether, this study provides an expanded overview of various rare immune cell subtypes in MGM and demonstrates their integration into different prognostic immune ecotypes, enabling better stratification in future clinical studies.
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