Oncological Pathology and Bioinformatics Research Group, Molecular Biology and Research Section, Pathology Department, Hospital de Tortosa Verge de la Cinta, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Esplanetes, 14, 43500 Tortosa, Spain.
Clinical Studies Unit, Hospital de Tortosa Verge de la Cinta, Carretera Esplanetes, 14, 43500 Tortosa, Spain.
Int J Mol Sci. 2023 Jul 11;24(14):11297. doi: 10.3390/ijms241411297.
Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.
三阴性乳腺癌（TNBC）由于对治疗的反应较弱或缺乏反应以及预后较差而特别具有挑战性。新辅助化疗（NAC）反应的有效性受到肿瘤微环境（TME）元素变化的强烈影响。这项工作旨在使用免疫组织化学和原位杂交技术来描述 96 例 TNBC 患者的残留 TME 成分，并评估其对部分缓解者与无缓解者的预后意义。与无反应者相比，部分缓解者中含有更高水平的 CD83+成熟树突状细胞、FOXP3+调节性 T 细胞和 IL-15 表达，但 CD138+细胞浓度较低，其 OS 和 RFS 更好。然而，除了肿瘤直径和诊断时的阳性淋巴结状态外，残留 TME 中的基质金属蛋白酶-9（MMP-9）表达被确定为与 NAC 反应不良相关的独立因素。这项研究深入了解了残留肿瘤床的关键组成部分，例如 MMP-9，它与对 NAC 缺乏病理反应密切相关。这些知识可能有助于早期识别不太可能对 NAC 有反应的 TNBC 患者，并允许建立新的治疗靶点。
