Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128 Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy.
Cells. 2021 Jan 23;10(2):223. doi: 10.3390/cells10020223.
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.
近几十年来，人们对免疫疗法领域的兴趣日益浓厚，这促使人们对乳腺癌（BC）免疫微环境进行了深入研究。在这种情况下，肿瘤浸润淋巴细胞（TILs）已成为一种具有临床相关性且高度可重复的生物标志物，能够影响 BC 的预后和对治疗的反应。事实上，在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 患者中，对原发肿瘤中 TILs 的评估被证明具有很强的预后意义，因此在这一背景下获得了 1b 级证据。此外，在所有 BC 亚型中均报道了 TILs 与新辅助化疗后病理完全缓解之间存在很强的相关性，并且在早期 HER2 阳性乳腺癌患者中，TILs 较高也显示出了预后作用。FDA 批准的检测方法将首个免疫检查点抑制剂引入 PD-L1 阳性状态的晚期 TNBC 治疗武器库后，对 BC 免疫浸润的兴趣进一步增加。然而，尽管取得了这些进展，但仍然缺乏一种能够可靠且详尽地预测 BC 免疫疗法获益的生物标志物，这突显了进一步深入研究这一问题的必要性。最后，更全面地评估免疫浸润，包括肿瘤浸润免疫细胞的数量和质量，并将 TILs 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/或机器学习的平台对 BC 免疫浸润进行更全面的描述，这些都是很有前途的策略，有可能优化研究领域患者的选择和分层。在本综述中，我们总结了 BC 中免疫浸润的现有证据和最新进展，重点介绍了当前的临床应用、潜在的临床意义和主要的未解决问题。
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