Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, Washington.
New York University School of Medicine, Perlmutter Cancer Center, New York.
JAMA Oncol. 2016 Oct 1;2(10):1354-1360. doi: 10.1001/jamaoncol.2016.1061.
The presence of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in breast cancer, and TILs may synergize with chemotherapy and immune checkpoint inhibitor therapy for improved clinical response. A more detailed understanding of the variation in lymphocytic infiltration in breast cancer may aid in identifying subtypes more amenable to immunomodulation.
To determine the median percentage of patients with breast cancer with no, intermediate, or high levels of TIL and assess variations in lymphocytic cell subsets across breast cancer subtypes.
Eligible studies (PubMed, 1990-2015) analyzed tumor lymphocytic, CD8+, and FOXP3+ cellular infiltrates, and used multivariable analyses and quantitative methods for enumerating cell populations. Selection of of studies was performed in accordance with PRISMA guidelines and evaluated by 2 independent appraisers.
Fifteen studies (n = 13 914) met prespecified criteria and were reviewed in December 2015. A median of 11% (range, 5%-26%) of breast cancers demonstrate lymphocyte-predominant breast cancer (LPBC), with approximately 16% of cancers showing no evidence of TILs. Triple-negative (TN) breast cancers demonstrated the highest incidence of LPBC (20%; range, 4%-37%). This incidence is similar to that of breast cancers that are human epidermal growth factor 2 positive and either hormone receptor positive or negative (HER2+) at 16% (range 11%-24%). Hormone receptor positive/HER2- (HR+) breast cancer showed the lowest incidence of LPBC at 6% (range, 3%-12%). CD8+ T-cell infiltrates, indicative of type I immunity, were found in 48% of all breast cancers (range, 32%-80%) with similar levels observed in TN (60%; range, 40%-91%) and HER2+ disease (61%; range, 40%-83%). Fewer HR+ tumors demonstrated CD8+ TIL (43%; range, 30%-73%). The highest levels of FOXP3+ cells were observed in TN (70%; range, 65%-76%) and HER2+ disease (67%; range, 61%-74%). A minority of HR+ breast cancers demonstrated high levels of tumor-infiltrating FOXP3+ cells (38%; range, 35%-41%).
The magnitude of TIL is variable within and between breast cancer subtypes. Levels of lymphocytic subpopulations may identify breast cancers more amenable to immunomodulation and indicate additional strategies to enhance immunity in patients with low to moderate levels of TILs.
背景：肿瘤浸润淋巴细胞（TILs）的存在是乳腺癌的一个有利预后因素，并且 TILs 可能与化疗和免疫检查点抑制剂治疗协同作用，以提高临床反应。更详细地了解乳腺癌中淋巴细胞浸润的变化可能有助于确定更适合免疫调节的亚型。
目的：确定乳腺癌患者中无、中、高水平 TIL 的中位数百分比，并评估淋巴细胞亚群在乳腺癌亚型中的变化。
证据回顾：符合条件的研究（PubMed，1990-2015 年）分析了肿瘤淋巴细胞、CD8+和 FOXP3+细胞浸润，并使用多变量分析和定量方法对细胞群体进行计数。研究的选择符合 PRISMA 指南，并由 2 位独立评估者进行评估。
发现：15 项研究（n=13914）符合既定标准，并于 2015 年 12 月进行了审查。中位数 11%（范围，5%-26%）的乳腺癌表现为淋巴细胞优势型乳腺癌（LPBC），约 16%的癌症无 TILs 证据。三阴性（TN）乳腺癌的 LPBC 发生率最高（20%；范围，4%-37%）。这一发生率与人类表皮生长因子 2 阳性且激素受体阳性或阴性（HER2+）的乳腺癌相似（16%；范围，11%-24%）。激素受体阳性/HER2-（HR+）乳腺癌的 LPBC 发生率最低，为 6%（范围，3%-12%）。CD8+T 细胞浸润，提示 I 型免疫，在所有乳腺癌中占 48%（范围，32%-80%），TN（60%；范围，40%-91%）和 HER2+疾病（61%；范围，40%-83%）的水平相似。较少的 HR+肿瘤显示 CD8+TIL（43%；范围，30%-73%）。TN（70%；范围，65%-76%）和 HER2+疾病（67%；范围，61%-74%）中观察到最高水平的 FOXP3+细胞。少数 HR+乳腺癌表现出高水平的肿瘤浸润 FOXP3+细胞（38%；范围，35%-41%）。
结论：TIL 的数量在乳腺癌亚型内和之间存在差异。淋巴细胞亚群的水平可能确定更适合免疫调节的乳腺癌，并表明在 TIL 水平较低或中等的患者中增强免疫的额外策略。
