In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. In the present review, we summarize available evidence and recent updates on immune infiltrates in BC, focusing on current clinical applications, potential clinical implications and major unresolved issues.

中文翻译：

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乳腺癌中的免疫浸润：最新进展和临床意义

近几十年来，人们对免疫治疗领域日益浓厚的兴趣促进了对乳腺癌（BC）免疫微环境的深入研究。在这种背景下，肿瘤浸润淋巴细胞 (TIL) 已成为一种临床相关且高度可重复的生物标志物，能够影响 BC 预后和治疗反应。事实上，TIL 对原发肿瘤的评估被证明对接受辅助或新辅助化疗的三阴性 (TN) BC 患者以及未接受任何全身治疗的早期 TNBC 患者具有很强的预后作用，从而获得了 1b 级证据在这个设置中。此外，据报道，在所有 BC 亚型中，TIL 与新辅助化疗后的病理完全缓解之间存在密切关系，并且较高的 TIL 在早期 HER2 阳性乳腺癌患者中的预后作用也已得到证实。通过 FDA 批准的检测，在晚期 TNBC 患者的治疗设备中引入首个免疫检查点抑制剂，进一步激发了人们对 BC 免疫浸润的兴趣。然而，尽管取得了这些进展，但仍然缺乏能够可靠、详尽地预测 BC 免疫治疗获益的生物标志物，这凸显了进一步深化这一问题的迫切需要。最后，对免疫浸润进行更全面的评估，整合肿瘤浸润免疫细胞的数量和质量，并将 TIL 纳入包含其他临床或生物学相关生物标志物的综合评分，以及采用基于软件和/或机器学习平台为了更全面地表征 BC 免疫浸润，正在成为有前景的策略，有可能优化研究领域的患者选择和分层。在本综述中，我们总结了 BC 免疫浸润的现有证据和最新更新，重点关注当前的临床应用、潜在的临床影响和主要未解决的问题。