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:Mature Tertiary Lymphoid Structures Indicate Good Chemotherapy Response and Prognosis in Advanced Colorectal Cancer.
Mature Tertiary Lymphoid Structures Indicate Good Chemotherapy Response and Prognosis in Advanced Colorectal Cancer.
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成熟 TLS 可能通过免疫活性促进化疗疗效。原发肿瘤中 TLS 的成熟度可能代表一种新型生物标志物,用于预测晚期 CRC 中原发灶和转移灶的全身化疗反应和免疫状态。
三级淋巴结构(TLS)是包括B细胞和T细胞在内的免疫细胞簇,参与抗肿瘤免疫,并在多种恶性肿瘤中与良好预后相关,但其与全身化疗的关联尚不清楚。我们研究了TLS作为预测晚期结直肠癌(CRC)化疗疗效的生物标志物的作用。
我们分析了78例转移性或复发性CRC病例,这些病例在化疗前均有未经治疗的切除原发肿瘤标本可用。通过免疫组化评估TLS成熟度,定义为生发中心中存在CD23+ B细胞,并分析其与临床病理特征、治疗反应、TIL(肿瘤浸润淋巴细胞)及预后的关系。在11例切除转移灶的病例中,分析TIL(肿瘤浸润淋巴细胞),以探讨原发肿瘤中TLS成熟度与远处部位免疫状态之间的关系。
成熟TLS阴性组的化疗敏感性、无进展生存期和总生存期均较差。多因素分析证实,TLS成熟度是该队列中治疗反应和生存结局的独立预测因素。成熟TLS与原发肿瘤和转移肿瘤中更高的CD3+和CD8+T细胞浸润相关。
Tertiary lymphoid structures (TLS), clusters of immune cells including B and T cells, are involved in anti-tumor immunity and correlate with a favorable prognosis in several malignancies, but their association with systemic chemotherapy is unknown. We investigated the role of TLS as a biomarker for predicting chemotherapy efficacy in advanced colorectal cancer (CRC).
We analyzed 78 CRC cases with metastatic or recurrent lesions, in which untreated resected primary tumors were available before chemotherapy. TLS maturity, defined by the presence of CD23 + B cells in germinal centers, was assessed by immunohistochemistry and evaluated in relation to clinicopathological features, treatment response, tumor-infiltrating lymphocytes, and prognosis. In 11 cases with resected metastatic lesions, tumor-infiltrating lymphocytes were analyzed to explore the relationship between TLS maturity in primary tumors and immune status at distant sites.
Mature TLS-negative groups had poorer chemotherapy sensitivity, progression-free survival, and overall survival. Multivariate analysis confirmed TLS maturity as an independent predictor of both therapeutic response and survival outcomes in this cohort. Mature TLS was associated with higher CD3 + and CD8 + T-cell infiltration in both primary and metastatic tumors.
Mature TLS may contribute to favorable chemotherapeutic efficacy through immune activity. TLS maturity in primary tumors may represent a novel biomarker for predicting systemic chemotherapy response and immune status across primary and metastatic sites in advanced CRC.
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