Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included. The analysis demonstrated a distinct expression pattern among breast cancer subtypes characterized by increased CD8 + , CD163 + and CD163 + PD-L1 + cells along with high PD-L1 status and decreased fraction of CD8 + Ki67 + T cells in triple negative (TNBC) and HER2 + compared to luminal tumors. Kaplan–Meier and Cox univariate survival analysis revealed that breast cancer patients with high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + cells, PD-L1 score and CD163 + PD-L1 + cells are likely to have a prolonged relapse free survival, while patients with high CD163 + cells have a worse prognosis. A differential impact of high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + T cells, CD163 + PD-L1 + macrophages and PD-L1 status on prognosis was identified among the various breast cancer subtypes since only TNBC patients experience an improved prognosis compared to patients with luminal A tumors. Conversely, high infiltration by CD163 + cells is associated with worse prognosis only in patients with luminal A but not in TNBC tumors. Multivariate Cox regression analysis in TNBC patients revealed that increased CD8 + [hazard ratio (HR) = 0.542; 95% confidence interval (CI) 0.309–0.950; p = 0.032), CD8 + TCF1 + (HR = 0.280; 95% CI 0.101–0.779; p = 0.015), CD163 + PD-L1 + (HR: 0.312; 95% CI 0.112–0.870; p = 0.026) cells along with PD-L1 status employing two different scoring methods (HR: 0.362; 95% CI 0.162–0.812; p = 0.014 and HR: 0.395; 95% CI 0.176–0.884; p = 0.024) were independently linked with a lower relapse rate. Multivariate analysis in Luminal type A patients revealed that increased CD163 + was independently associated with a higher relapse rate (HR = 2.360; 95% CI 1.077–5.170; p = 0.032). This study demonstrates that the evaluation of the functional status of CD8 + T cells in combination with the analysis of immunosuppressive elements could provide clinically relevant information in different breast cancer subtypes.

乳腺癌微环境的免疫表型分析作为改善乳腺癌患者分层的临床工具越来越受到关注。本研究的目的是评估不同乳腺癌亚型中增殖的 CD8 +（包括 CD8 + TCF1 + Τ 细胞）以及表达 PD-L1 的组织相关巨噬细胞。纳入了由 791 名未接受过治疗的乳腺癌患者组成的特征明确的队列。分析表明乳腺癌亚型之间存在独特的表达模式，其特征是 CD8 + 、CD163 + 和 CD163 + PD-L1 + 细胞增加，PD-L1 状态较高，三阴性 (TNBC) 中 CD8 + Ki67 + T 细胞比例减少和 HER2 + 与管腔肿瘤相比。 Kaplan-Meier 和 Cox 单变量生存分析显示，具有高 CD8 + 、CD8 + Ki67 + 、CD8 + TCF1 + 细胞、PD-L1 评分和 CD163 + PD-L1 + 细胞的乳腺癌患者可能具有较长的无复发生存期，而CD163+细胞高的患者预后较差。在各种乳腺癌亚型中，高 CD8 + 、CD8 + Ki67 + 、CD8 + TCF1 + T 细胞、CD163 + PD-L1 + 巨噬细胞和 PD-L1 状态对预后的影响不同，因为只有 TNBC 患者的预后有所改善与管腔 A 肿瘤患者相比。相反，CD163 + 细胞的高浸润仅在 Luminal A 患者中与较差的预后相关，但在 TNBC 肿瘤中则不然。 TNBC 患者的多变量 Cox 回归分析显示，CD8 + 增加 [风险比 (HR) = 0.542； 95% 置信区间 (CI) 0.309–0.950； p = 0.032）、CD8 + TCF1 +（HR = 0.280；95% CI 0.101–0.779； p = 0.015）、CD163 + PD-L1 +（HR：0.312；95% CI 0.112–0.870； p = 0。026）细胞以及采用两种不同评分方法的 PD-L1 状态（HR：0.362；95% CI 0.162–0.812； p = 0.014 和 HR：0.395；95% CI 0.176–0.884； p = 0.024）与复发率较低。 Luminal A 型患者的多变量分析显示，CD163 + 升高与较高的复发率独立相关（HR = 2.360；95% CI 1.077–5.170； p = 0.032）。本研究表明，CD8+T细胞功能状态的评估结合免疫抑制元件的分析可以提供不同乳腺癌亚型的临床相关信息。