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 density and distribution in breast cancer: A two-year study on their clinicopathological correlation.
Tumor-infiltrating lymphocytes density and distribution in breast cancer: A two-year study on their clinicopathological correlation.
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本研究证实 sTILs 与 iTILs 之间存在强相关性,提示在常规实践中单独评估 sTIL 可能已足够。较高的 TIL 水平与更具侵袭性的病理特征显著相关,如更高的肿瘤分级和三阴性/HER2 富集亚型。虽然 TIL 水平随临床分期而变化,但未观察到一致的单调关系。未来研究应整合其他可预测免疫治疗反应的生物标志物,并建立具有临床可操作性的 TIL 截断值。
TIL(肿瘤浸润淋巴细胞)(TILs)正逐渐成为浸润性乳腺癌(IBC)的关键生物标志物,反映宿主免疫反应并影响预后。尽管TILs在全球范围内已被广泛研究,但来自印度次大陆的数据仍然匮乏。本研究评估了印度队列中的间质TILs(sTILs)和瘤内TILs(iTILs),探讨其与病理特征、临床分期及分子亚型的关联。
一项在印度单一癌症中心进行的回顾性观察研究,连续纳入两年内的IBC患者。收集了人口学、病理学和免疫组化(IHC)数据(雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2 [HER2]、Ki67增殖指数)。TILs在苏木精和伊红(H and E)切片上使用国际TILs工作组(ITILWG)指南进行评估:sTILs表示为基质面积的百分比,iTILs为半定量(0-300)。使用Spearman秩相关、Kruskal-Wallis检验和多变量线性回归分析相关性和组间比较。
共纳入326例患者。中位sTIL百分比为7%(四分位距[IQR] 5-38),中位iTIL评分为60(IQR 20-130)。在三阴性和HER2富集型肿瘤、高级别癌症以及激素受体阴性病变中观察到更高的中位sTIL和iTIL水平。中位sTIL百分比随肿瘤分级升高而增加(1级:5% [IQR 5-5];3级:35% [IQR 9-60])。iTIL也观察到类似模式。经Holm校正后,与核多形性、核分裂活性、肿瘤分级、分子亚型、Ki-67类别和激素受体状态的关联仍具有统计学显著性。在使用对数转换TIL的多变量分析中,分子亚型和肿瘤分级与更高的sTIL和iTIL水平独立相关,而IV期疾病与II期相比与更低的TIL水平相关。
A retrospective observational study of consecutive IBC patients at a single Indian cancer center was conducted over two years and included. Demographic, pathological, and immunohistochemical (IHC) data (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 [HER2], Ki67 proliferation index) were collected. TILs were evaluated on Hematoxylin and eosin (H and E) slides using International TILs Working Group (ITILWG) guidelines: sTILs expressed as a percentage of stromal area and iTILs semi-quantitatively (0-300). Correlations and group comparisons were analyzed using Spearman's rank correlation, Kruskal-Wallis tests, and multivariable linear regression.
A total of 326 patients were included. The median sTIL percentage was 7% (interquartile range [IQR] 5-38), and the median iTIL score was 60 (IQR 20-130). Higher median sTIL and iTIL levels were observed in triple-negative and HER2-enriched tumors, high-grade cancers, and hormone receptor-negative disease. Median sTIL percentages increased with tumor grade (grade 1: 5% [IQR 5-5]; grade 3: 35% [IQR 9-60]). Similar patterns were observed for iTILs. After Holm adjustment, associations with nuclear pleomorphism, mitotic activity, tumor grade, molecular subtype, Ki-67 category, and hormone receptor status remained statistically significant. In multivariable analyses using log-transformed TILs, molecular subtype and tumor grade were independently associated with higher sTIL and iTIL levels, while stage IV disease was associated with lower TIL levels compared with stage II.
This study confirms a strong correlation between sTILs and iTILs, suggesting sTIL assessment alone may suffice for routine practice. Higher TIL levels were significantly linked to more aggressive pathological features, such as higher tumor grade and triple-negative/HER2-enriched subtypes. While TIL levels varied with clinical stage, no consistent monotonic relationship was observed. Future research should integrate other biomarkers predictive of immunotherapy response and establish clinically actionable TIL cut-off values.
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