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.
Highlights
Increasing evidence indicates that the interplay between the immune system and cancer cells is critical for tumor progression [1, 2]
The results showed that the pathological complete response (pCR) rate for patients with breast cancer was significantly higher for patients in the high tumor-infiltrating lymphocytes (TILs) group than those in the low TIL group (OR, 2.81; 95% confidence intervals (CIs), 2.02–3.91, P < 0.001; Figure 3)
We assessed 23 studies that evaluated the usefulness of TILs in predicting the pCR rate after primary chemotherapy as well as predicting prognosis
Summary
Increasing evidence indicates that the interplay between the immune system and cancer cells is critical for tumor progression [1, 2]. The ability to induce cell death might be critical for long-lasting tumor remission. In this way, conventional cytotoxic chemotherapy serves as a form of immunotherapy. Many recent larger studies have focused mainly on TILs that clinically respond to anthracycline- or taxinol-based therapy, in which patients were categorized by TIL group [8,9,10,11]. These studies might help us further understand breast cancer and explain the clinical usefulness of TILs as predictive markers. We identified the association between TILs and short-term clinical response to therapy and survival in patients with breast cancer
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have