Breast cancer remains a formidable global health challenge, with triple-negative breast cancer (TNBC) posing unique clinical complexities. Characterized by its aggressive nature and limited number of specific therapeutic targets, this breast cancer subtype disproportionately affects African American women, highlighting critical disparities in care. The tumor immune microenvironment (TIME) plays a critical role in breast cancer development and response to immunotherapy, and it is essential in fostering an immunosuppressive and pro-inflammatory niche. Inflammation, primarily mediated by the NF-κB signaling pathway and chemokine signaling, particularly involving CCL2, plays a pivotal role in TNBC progression and therapy resistance. This review describes some of the molecular mechanisms of polyphenols, which are naturally occurring compounds abundant in various dietary sources, and their potential use as therapeutic agents in the management of TNBC. Polyphenolic compounds have been described as modulating the TIME through the inhibition of tumor progression, immune evasion, and therapy resistance, due to their diverse bioactivities, including anti-inflammatory, antioxidant, and anticancer properties, making them attractive candidates for combating the aggressiveness of TNBC and addressing treatment disparities. Polyphenols, such as curcumin, gossypol, butein, epigallocatechin gallate, cardamonin, and resveratrol, have demonstrated efficacy in modulating several signaling pathways within the TIME, which are implicated in the progression of TNBC. This review highlights the potential effects of polyphenols on inflammatory cytokine release, programmed cell death ligand 1 (PD-L1) expression, which is associated with immune evasion by the host cell, and various intracellular signaling cascades, demonstrating their potential use in personalized therapeutic interventions for TNBC. This study also describes differential responses of TNBC cell lines to polyphenol treatment, highlighting the importance of considering genetic variability in therapeutic strategies, as well as the importance of the interaction of polyphenols with the gut microbiome, which may establish the bioavailability and effectiveness of these compounds toward therapeutic outcomes. Further preclinical and clinical studies are warranted to fully elucidate the therapeutic potential of polyphenols and translate these findings into clinical practice, thereby improving outcomes for patients with TNBC worldwide.
乳腺癌仍是全球健康领域一项严峻挑战，其中三阴性乳腺癌（TNBC）因其独特的临床复杂性尤为突出。该亚型以侵袭性强、特异性治疗靶点有限为特征，且对非裔美国女性的影响尤为显著，凸显了医疗领域存在的关键差异。肿瘤免疫微环境（TIME）在乳腺癌发展及免疫治疗应答中起着关键作用，对形成免疫抑制和促炎性微环境至关重要。炎症主要通过NF-κB信号通路和趋化因子信号（特别是CCL2介导）发挥作用，在TNBC进展和治疗抵抗中具有核心地位。本综述阐述了多酚类物质的分子机制及其作为TNBC治疗药物的潜在价值。多酚类化合物广泛存在于各类膳食来源中，因其抗炎、抗氧化和抗癌等多重生物活性，可通过抑制肿瘤进展、免疫逃逸和治疗抵抗来调节TIME，成为对抗TNBC侵袭性和解决治疗差异的理想候选物质。姜黄素、棉酚、紫铆因、表没食子儿茶素没食子酸酯、豆蔻明和白藜芦醇等多酚类物质已证实能有效调节TIME中与TNBC进展相关的多条信号通路。本综述重点探讨了多酚类物质对炎症因子释放、程序性死亡配体1（PD-L1）表达（与宿主细胞免疫逃逸相关）及多种细胞内信号级联反应的潜在影响，揭示了其在TNBC个体化治疗干预中的应用前景。研究还阐述了TNBC细胞系对多酚治疗的不同反应，强调了在治疗策略中考虑遗传变异的重要性，以及多酚与肠道微生物组相互作用的关键性——这种相互作用可能决定这些化合物的生物利用度和治疗效果。未来需要开展更多临床前及临床研究，以充分阐明多酚的治疗潜力，并将研究成果转化为临床实践，从而改善全球TNBC患者的治疗结局。
肿瘤(癌症)患者之家