Wang Ke, Xu Jianjun, Zhang Tao, Xue Dan
Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
School of Finance, Zhejiang University of Finance and Economics, Hangzhou, 310018, China.
Oncotarget. 2016 Jul 12;7(28):44288-44298. doi: 10.18632/oncotarget.9988.
Tumor-infiltrating lymphocytes (TILs) influence tumor prognosis and the chemotherapeutic response. Here, we quantified the clinical relevance of TILs, including the effect of TILs on lymphocyte subpopulations and assessed their consistency in breast cancer. We searched published literature from January 2000 to January 2016. The main parameters analyzed were pathological complete response (pCR) and survival outcome following chemotherapy in patients with breast cancer. Pooled odds ratio (OR) or relative risk (RR) values with 95% confidence intervals (CIs) were computed using random and fixed-effects models. Subgroup and heterogeneity analyses were also conducted. Twenty-three studies, which included 13,100 patients, met the inclusion criteria. The pooled results showed that TILs were associated with clinicopathological parameters of biologically aggressive phenotypes, such as high tumor grade or estrogen/progesterone receptor negativity, but they were not correlated with human epidermal growth factor receptor-2 expression. Moreover, a high TIL level was associated with a significantly improved pCR rate compared with a low TIL level (OR, 2.81; P < 0.001), particularly in the triple-negative breast cancer subtype (OR, 4.67; P < 0.001). An analysis of lymphocyte subpopulations showed that infiltration by CD8 lymphocytes, but not by CD4 lymphocytes and Foxp3 cells, was associated with a high pCR rate. Furthermore, a high TIL level was associated with significantly longer disease-free survival and overall survival. Our present meta-analysis indicates that an increased number of TILs predicted pCR to chemotherapy and improved survival. A high TIL level, characterized mainly by the infiltration of CD8 lymphocytes, is a strong predictive and prognostic factor.
肿瘤浸润淋巴细胞（TILs）会影响肿瘤预后及化疗反应。在此，我们量化了TILs的临床相关性，包括TILs对淋巴细胞亚群的影响，并评估了它们在乳腺癌中的一致性。我们检索了2000年1月至2016年1月期间发表的文献。分析的主要参数为乳腺癌患者化疗后的病理完全缓解（pCR）和生存结果。使用随机和固定效应模型计算合并比值比（OR）或相对风险（RR）值及95%置信区间（CIs）。还进行了亚组分析和异质性分析。23项研究（包括13100例患者）符合纳入标准。汇总结果显示，TILs与生物学侵袭性表型的临床病理参数相关，如高肿瘤分级或雌激素/孕激素受体阴性，但与人类表皮生长因子受体2表达无关。此外，与低TIL水平相比，高TIL水平与显著提高的pCR率相关（OR，2.81；P<0.001），特别是在三阴性乳腺癌亚型中（OR，4.67；P<0.001）。淋巴细胞亚群分析表明，CD8淋巴细胞浸润而非CD4淋巴细胞和Foxp3细胞浸润与高pCR率相关。此外，高TIL水平与显著更长的无病生存期和总生存期相关。我们目前的荟萃分析表明，TILs数量增加预示着化疗的pCR并改善了生存。以CD8淋巴细胞浸润为主的高TIL水平是一个强有力的预测和预后因素。
