新辅助化疗（NACT）期间免疫浸润的早期变化与三阴性乳腺癌（TNBC）的病理完全反应（pCR）之间的关系仍未得到探索。
对来自西德研究组辅助动态标记调整个性化治疗试验优化早期乳腺癌风险评估和治疗反应预测-三阴性乳腺癌（WSG-ADAPT-TN）试验的66名患者在基线和NACT3周后获得的匹配肿瘤活检进行多重免疫组织化学。CD4，CD8，CD73，T细胞，PD1阳性CD4和CD8细胞，和基线时基质和/或肿瘤中的PDL1水平，使用单变量逻辑回归评估pCR的第3周和第3周变化。
与免疫细胞组成和功能标志物无变化相比，从“冷”过渡到“热”(基线时低于中位数和高于中位数标记水平，分别）提示PD1阳性CD4（肿瘤：OR=1.55，95％CI0.45至5.42；基质：OR=2.65，95％CI0.65至10.71）和PD1阳性CD8浸润（肿瘤：OR=1.77，95％CI0.60至5.20；基质：OR=1.25，95％CI0.41至3.84；肿瘤基质：OR=1.62，95％CI0.51）。在PD1阳性CD8细胞中“热到冷”转变后未观察到pCR。T细胞冷热转变后pCR率较低(肿瘤:OR=0.26,95%CI0.03至2.34;基质:OR=0.35,95%CI0.04至3.25;肿瘤+基质:OR=0.00,95%CI0.00至1.04)和PD1阳性CD4细胞(肿瘤:OR=0.60,95%CI0.11至3.35;基质:OR=0.22,95%CI=0.03至1.92);较高的pCR率与“改变的”分布(肿瘤和间质中低于中位数和高于中位数的水平，分别为T细胞（OR=3.50，95％CI0.84至14.56）和PD1阳性CD4细胞（OR=4.50，95％CI1.01至20.14）。
我们的探索性发现表明，对早期免疫浸润动力学的综合分析补充了目前研究的pCR的预测标志物，并可能有可能改善TNBC中个性化降级/升级策略的指导。
The association of early changes in the immune infiltrate during neoadjuvant chemotherapy (NACT) with pathological complete response (pCR) in triple-negative breast cancer (TNBC) remains unexplored.
Multiplexed immunohistochemistry was performed in matched tumor biopsies obtained at baseline and after 3 weeks of NACT from 66 patients from the West German
Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy
Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer (WSG-ADAPT-TN)
trial. Association between CD4, CD8, CD73, T cells, PD1-positive CD4 and CD8 cells, and PDL1 levels in stroma and/or tumor at baseline, week 3 and 3-week change with pCR was evaluated with univariable logistic regression.
Compared with no change in immune cell composition and functional markers, transition from \'cold\' to \'hot\' (below-median and above-median marker level at baseline, respectively) suggested higher pCR rates for PD1-positive CD4 (tumor: OR=1.55, 95% CI 0.45 to 5.42; stroma: OR=2.65, 95% CI 0.65 to 10.71) and PD1-positive CD8 infiltrates (tumor: OR=1.77, 95% CI 0.60 to 5.20; stroma: OR=1.25, 95% CI 0.41 to 3.84; tumor+stroma: OR=1.62, 95% CI 0.51 to 5.12). No pCR was observed after \'hot-to-cold\' transition in PD1-positive CD8 cells. pCR rates appeared lower after hot-to-cold transitions in T cells (tumor: OR=0.26, 95% CI 0.03 to 2.34; stroma: OR=0.35, 95% CI 0.04 to 3.25; tumor+stroma: OR=0.00, 95% CI 0.00 to 1.04) and PD1-positive CD4 cells (tumor: OR=0.60, 95% CI 0.11 to 3.35; stroma: OR=0.22, 95% CI 0.03 to 1.92; tumor+stroma: OR=0.32, 95% CI 0.04 to 2.94). Higher pCR rates collated with \'altered\' distribution (levels below-median and above-median in tumor and stroma, respectively) of T cell (OR=3.50, 95% CI 0.84 to 14.56) and PD1-positive CD4 cells (OR=4.50, 95% CI 1.01 to 20.14).
Our exploratory findings indicate that comprehensive analysis of early immune infiltrate dynamics complements currently investigated predictive markers for pCR and may have a potential to improve guidance for individualized de-escalation/escalation strategies in TNBC.
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