再分化使能的 TSHRCART 细胞克服侵袭性甲状腺癌中的抗原丢失
Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.
这些发现确立了肿瘤再分化作为一种可推广的策略,用于克服抗原丢失并增强 CAR-T 细胞疗法在甲状腺癌以及可能其他实体瘤中的疗效。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Infiltrating Lymphocytes as Mediators of the Obesity and Papillary Thyroid Carcinoma Lymph Node Metastasis Association: An Observational Retrospective Cohort Study.
Tumor-Infiltrating Lymphocytes as Mediators of the Obesity and Papillary Thyroid Carcinoma Lymph Node Metastasis Association: An Observational Retrospective Cohort Study.
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TIL 浸润可能影响肥胖相关的 PTC LNM。
肥胖会增加甲状腺乳头状癌(PTC)和淋巴结转移(LNM)风险,这可能是通过调节肿瘤免疫微环境实现的。
研究遵循STROCSS指南开展回顾性队列研究。通过二元逻辑回归和比值比(OR)分析TIL(肿瘤浸润淋巴细胞)、肥胖及LNM之间的关联。利用癌症基因组图谱(TCGA)数据,考察甲状腺癌组织中免疫细胞亚群与肥胖调节分子的关系。采用Cox风险模型分析甲状腺癌预后。
调整混杂因素后,研究发现超重和肥胖均与TIL浸润减少相关(OR分别为0.876,p=0.005;0.795,p=0.001),且与LNM可能性增加相关(OR分别为1.134,p=0.005;1.307,p<0.001)。相反,TIL浸润与LNM呈负相关(OR=0.868,p<0.001)。当单独将TIL浸润纳入控制变量时,肥胖与TIL浸润的组合并不能独立预测LNM(调整后OR=1.442,p=0.113);但肥胖本身仍会提高LNM可能性(调整后OR=1.539,p=0.02)。此外,TCGA数据分析显示,肥胖患者重要脂肪因子脂联素减少,且脂联素水平与浸润的树突细胞及调节性T细胞数量呈负相关。在PTC中,ADIPOR2表达与LNM呈负相关,并与不良预后相关;风险比为0.480(p=0.007)。
TIL浸润可能影响肥胖相关的PTC淋巴结转移。肥胖可能通过ADIPOR2调节抗肿瘤免疫细胞,影响LNM并导致预后不良。
Obesity increases the risk of papillary thyroid carcinoma (PTC) and lymph node metastasis (LNM), possibly via modulation of the tumor immunological microenvironment.
The STROCSS guideline was followed to conduct a retrospective cohort study. Binary logistic regression analysis with odds ratios (OR) was performed to assess the association between tumor-infiltrating lymphocytes (TILs), obesity, and LNM. Using The Cancer Genome Atlas (TCGA) data, we examined the relationship between immune cell subsets and obesity-regulating molecules in thyroid cancer tissues. The Cox regression risk model was used to analyze the prognosis of thyroid cancer.
After adjusting for confounding factors, our findings revealed that overweight and obesity were associated with a decrease in TIL infiltration (OR 0.876, p = 0.005 and OR 0.795, p = 0.001, respectively). Furthermore, these conditions were observed to be correlated with increased likelihood of LNM (OR 1.134, p = 0.005 and OR 1.307, p < 0.001, respectively). On the contrary, TIL infiltration was inversely associated with LNM (OR 0.868, p < 0.001). When controlling for TIL infiltration as the sole variable, the combination of obesity and TIL infiltration did not independently predict LNM (adjusted OR 1.442, p = 0.113). However, obesity alone was found to elevate the likelihood of LNM (adjusted OR 1.539, p = 0.02). Additionally, adiponectin (a crucial adipokine) was reduced in obesity and demonstrated a negative correlation with the abundance of infiltrated dendritic cells and regulatory T cells, as evidenced by TCGA data analysis. Furthermore, ADIPOR2 expression negatively correlated with LNM and positively associated with unfavorable prognosis in PTC, with a hazard ratio of 0.480 (p = 0.007).
TIL infiltration may affect obesity-associated PTC LNM. Obesity may affect LNM and result in poor prognosis through ADIPOR2 regulation of antitumor immune cells.
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