Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis

Abstract

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.

Expression of T-Lymphocyte Markers in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

“…In the present study, mRNA expression of CD4, CD8, and FOXP3 was not different according to HER2 status of the TCGA dataset, but there was a significant correlation between T-cell markers. In addition, previous evidence have supported the prognostic and predictive roles of TILs in breast cancers [13142223]. Our study also suggested a possible prognostic role of T-lymphocyte markers measured at mRNA levels in HER2-positive tumors.…”

Heterogeneity of tumour‐infiltrating lymphocytes in breast cancer and its prognostic significance

“…There is a growing interest in quantifying and reporting total TILs in BC and their different subpopulations in clinical practice, owing to their prognostic and possibly predictive value for immunotherapies. 23,24 In this study, a large cohort with long-term clinical follow-up was used to assess the expression pattern of different immune cell subtypes in BC as well as their association with patient outcome and tumour progression.…”

Breast cancer intratumour heterogeneity: current status and clinical implications

“…In contrast, FOXP3+ cells were associated with a worse prognosis, and have been reported to be correlated with intratumour and tumour‐adjacent stromal compartments . Moreover, the distribution and prognostic significance of TILs is variable among BC molecular classes; they have significant prognostic value in the HER2‐positive and triple‐negative/basal‐like BC class, but not in ER‐positive luminal tumours …”

“…31 Moreover, the distribution and prognostic significance of TILs is variable among BC molecular classes; they have significant prognostic value in the HER2-positive and triple-negative/basallike BC class, but not in ER-positive luminal tumours. 32,33…”