The tumor microenvironment, composed of pro- and antitumor immune cells, affects cancer cell behavior. We aimed to evaluate whether tumor-infiltrating lymphocyte (TIL) density and TIL subtypes in core biopsies at the diagnosis of breast cancer patients could predict a pathologic complete response (pCR; ypT0/is ypN0) from neoadjuvant systemic therapy (NST). The TIL subtypes were determined based on the proportions of presumably antitumor (CD8+, CXCL13+) and protumor (PD-1+, FOXP3+) immune cells. A prospective, noninterventional study, including 171 participants undergoing NST, was performed. The median TIL density for the entire cohort was 10% (IQR: 3.5–23.8), and 59 (35%) patients achieved pCR. TIL density was positively associated with pCR (univariately and multivariably). In the multivariable logistic regression model, TIL density was an independent predictor of pCR (p= 0.012, OR 1.27; 95% CI 1.05–1.54) when controlled for age (p= 0.232), Ki-67 (p= 0.001), node-negative status (p= 0.024), and HER2+/triple negative vs. luminal B-like subtype (p< 0.001). In our sample, higher proportions of PD-1+ TILs and FOXP3+ TILs were associated with a higher probability of pCR but the association was not statistically significant and we could not make any conclusions on the direction of associations in the model with all four biomarkers. In the exploratory multivariable analysis, we showed that only higher CD8+ TILs were associated with pCR. In conclusion, TIL density and its subtypes are associated with pCR.
肿瘤微环境由促肿瘤和抗肿瘤免疫细胞构成，可影响癌细胞行为。本研究旨在评估乳腺癌患者确诊时穿刺活检标本中肿瘤浸润淋巴细胞密度及其亚型能否预测新辅助系统治疗后病理完全缓解情况。TIL亚型根据推定抗肿瘤免疫细胞与促肿瘤免疫细胞的比例进行界定。我们开展了一项前瞻性非干预性研究，纳入171例接受新辅助系统治疗的患者。全队列TIL密度中位值为10%，其中59例患者达到病理完全缓解。单变量及多变量分析均显示TIL密度与病理完全缓解呈正相关。在多变量逻辑回归模型中，在控制年龄、Ki-67指数、淋巴结阴性状态及HER2阳性/三阴性对比管腔B样亚型等因素后，TIL密度仍是病理完全缓解的独立预测因子。本研究中，PD-1阳性与FOXP3阳性TIL比例升高与病理完全缓解概率增加存在关联趋势，但未达统计学显著性，且无法在包含四种生物标志物的模型中确定关联方向。探索性多变量分析显示，仅CD8阳性TIL比例升高与病理完全缓解相关。综上所述，TIL密度及其亚型与病理完全缓解存在关联。
肿瘤(癌症)患者之家