The immune microenvironment (IME) of triple-negative breast cancers (TNBCs) and its modulation by neoadjuvant chemotherapy (NACT) remain to be fully characterized. Our current study aims to evaluate NACT-induced IME changes and assess the prognostic value of specific immune biomarkers. Tumor-infiltrating lymphocytes (TILs) were identified from hematoxylin-eosin-stained sections of paired pre- and post-NACT tumor samples from a TNBC cohort (n = 66) and expression of PD-L1, TIM-3, and LAG-3 evaluated by immunohistochemistry. Overall TIL counts and PD-L1 expression did not differ pre- and post-NACT, but there was a response-specific statistically significant difference. TIL counts decreased in 65.5% of patients who achieved a pathological complete response (pCR) and increased in 56.8% of no-pCR patients (p = 0.0092). PD-L1 expression was significantly more frequently lost after NACT in pCR than in no-pCR patients (41.4% vs 16.2%, p = 0.0020). TIM-3 positivity (≥ 1%) was significantly more frequent after NACT (p < 0.0001) with increases in expression levels occurring more frequently in no-pCR than in pCR patients (51.4% vs 31%). LAG-3 expression significantly decreased after NACT, but there was no difference between response groups. Before NACT, a high TIL count (> 10%) was significantly associated with better overall survival (OS), p = 0.0112. After NACT, PD-L1 positivity and strong TIM-3 positivity (≥ 5%) were both associated with significantly worse OS (p = 0.0055 and p = 0.0274, respectively). Patients positive for both PD-L1 and TIM-3 had the worst prognosis (p = 0.0020), even when only considering patients who failed to achieve a pCR, p = 0.0479. NACT induces significant IME changes in TNBCs. PD-L1 and TIM-3 expression post-NACT may yield important prognostic information for TNBC patients.

中文翻译：

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三阴性乳腺癌新辅助化疗引起的免疫微环境变化：MIMOSA-1 研究

三阴性乳腺癌 (TNBC) 的免疫微环境 (IME) 及其通过新辅助化疗 (NACT) 的调节仍有待充分表征。我们目前的研究旨在评估 NACT 诱导的 IME 变化并评估特定免疫生物标志物的预后价值。从 TNBC 队列（n = 66）和 PD-L1、TIM-3 和 LAG-3 的表达配对的 NACT 前和 NACT 后肿瘤样本的苏木精-伊红染色切片中鉴定出肿瘤浸润淋巴细胞 (TIL)通过免疫组织化学评估。总体 TIL 计数和 PD-L1 表达在 NACT 前后没有差异，但存在响应特异性的统计学显着差异。TIL 计数在 65.5% 的达到病理完全反应 (pCR) 的患者中减少，而在 56.8% 的无 pCR 患者中增加 (p = 0.0092)。与无 pCR 患者相比，pCR 患者 NACT 后 PD-L1 表达丢失的频率明显更高（41.4% 对 16.2%，p = 0.0020）。NACT 后 TIM-3 阳性（≥ 1%）明显更频繁（p < 0.0001），无 pCR 患者表达水平升高的频率高于 pCR 患者（51.4% vs 31%）。NACT 后 LAG-3 表达显着降低，但反应组之间没有差异。在 NACT 之前，高 TIL 计数 (> 10%) 与更好的总生存 (OS) 显着相关，p = 0.0112。NACT 后，PD-L1 阳性和 TIM-3 强阳性（≥ 5%）均与显着更差的 OS 相关（分别为 p = 0.0055 和 p = 0.0274）。PD-L1 和 TIM-3 均为阳性的患者预后最差（p = 0.0020），即使仅考虑未能达到 pCR 的患者，p = 0.0479。NACT 在 TNBC 中引起显着的 IME 变化。NACT 后的 PD-L1 和 TIM-3 表达可能为 TNBC 患者提供重要的预后信息。