单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer Microenvironment Defines Tumor-Infiltrating Lymphocyte Density and Tertiary Lymphoid Structure Formation in Laryngeal Cancer.
Cancer Microenvironment Defines Tumor-Infiltrating Lymphocyte Density and Tertiary Lymphoid Structure Formation in Laryngeal Cancer.
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免疫反应低下与缺氧背景和厌氧代谢有关,也与侵袭和转移能力增强有关。调节性 TIL 标志物与血管生成潜能增加相关。TIL 在临床实践中的预后、预测和治疗指导价值需要深入研究。
TIL(肿瘤浸润淋巴细胞)(TILs)的存在和活性是与抗肿瘤免疫应答相关的关键参数。大量研究揭示,TIL密度可作为预后标志物以及放疗、化疗和免疫治疗反应的预测因子。
我们检查了33例接受喉切除术的喉鳞状细胞癌(LSCC)中,浸润前沿和肿瘤内部间质中的TIL和三级淋巴结构TLS密度。TIL和TLS密度与厌氧代谢标志物、血管密度(VD)、血管存活能力(VSA)以及组织病理学参数进行了平行检测。
TIL 和 TLS 密度在内侧肿瘤区域显著降低(p < 0.0001)。侵袭性肿瘤前沿的 TIL 密度与淋巴结受累(p = 0.03)、HIF1 表达(p = 0.008)、血管密度(p = 0.02)和 MIB1(p = 0.006)呈负相关。内侧间质中的 TIL 密度与局部侵袭(边缘性 p = 0.05)、肿瘤出芽(TB)(p = 0.005)、MIB1(p = 0.02)和 HIF1 表达(p = 0.02)呈负相关。侵袭前沿和内侧肿瘤区域中低 TLS 密度与高 TB(分别为 p = 0.02 和 0.002)、HIF1(分别为 p = 0.003 和 0.01)和 LDH5 表达(分别为 p = 0.003 和 0.007)相关。CD4 +、FOXP3 + TIL 密度以及 FOXP3 + /CD8 + 比值与 VSA 直接相关(分别为 p = 0.008、0.02 和 0.05)。
The presence and activity of tumor-infiltrating lymphocytes (TILs) is a key parameter related to the antitumor immune response. A large number of studies reveal TIL density as a prognostic marker and predictor of response to radiotherapy, chemotherapy, and immunotherapy.
We examined the TIL and tertiary lymphoid structure TLS density in the invading front and inner tumor stroma, in a 33 squamous cell laryngeal carcinomas (LSCC) treated with laryngectomy. TIL and TLS densities were in parallel examined with markers of anaerobic metabolism, vascular density (VD), vascular survival ability (VSA), and histopathological parameters.
TIL and TLS densities significantly decreased in inner tumor areas (p < 0.0001). TIL density in the invading tumor front was inversely related with lymph node involvement (p = 0.03), HIF1 expression (p = 0.008), vessel density (p = 0.02), and MIB1 (p = 0.006). TIL density in inner stroma was inversely linked to local invasion (marginal p = 0.05), tumor budding (TB) (p = 0.005), MIB1 (p = 0.02), and HIF1 expression (p = 0.02). Low-TLS density in the invading front and in inner tumor areas was related to high TB (p = 0.02 and 0.002, respectively), HIF1 (p = 0.003 and 0.01, respectively), and LDH5 expression (p = 0.003 and 0.007, respectively). CD4 + , FOXP3 + TIL density, and FOXP3 + /CD8 + ratio were directly associated with VSA (p = 0.008, 0.02, and 0.05, respectively).
Poor immune response is related to hypoxic background and anaerobic metabolism, as well as increased invasive and metastatic ability. Regulatory TIL markers are linked with increased angiogenic potential. The prognostic, predictive, and therapy-guiding value of TILs in clinical practice demands thorough investigation.
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