Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer

Abstract

BackgroundThe presence of tumour-infiltrating lymphocytes (TILs) is a favourable prognostic factor in patients with early breast cancer. Programmed cell death-1 (PD-1) and its ligand PD-L1 are associated with a variety of adverse features. The purpose of this study was to clarify the relationships between TILs, PD-1 and PD-L1 as well as their prognostic implications in early breast cancer.MethodsWe investigated 180 patients with breast cancer who received neoadjuvant chemotherapy and underwent subsequent surgery for stage II–III invasive breast carcinoma between 1999 and 2007. TIL expression was classified as low or high using a previously reported scoring model. PD-1 and PD-L1 expression levels were determined by immunohistochemistry. The correlation between PD-1 expression in TILs and PD-L1 expression in cancer cells was also investigated.ResultsHigher tumour grade was significantly correlated with PD-L1 expression in tumours (p<0.0001). PD-1 and PD-L1 expression levels were associated with tumour subtype and were highest in triple-negative tumours (p<0.0001). Furthermore, expression of each of PD-1 and PD-L1 was significantly correlated with higher TIL expression and pathological complete response (pCR) (p<0.0001). PD-L1 expression in cancer cells was significantly correlated with PD-1 expression in TILs (p=0.03). The correlations between pCR and expression of each of PD-L1 and PD-1 were not significant.ConclusionExpression of PD-L1 and PD-1 in early breast cancer is associated with higher TIL scores and pCR; conversely, expression of these proteins correlates with poor prognostic clinicopathological factors such as tumour grade and subtype. TILs, PD-1 and PD-L1 can potentially predict the response to treatment.

PD‐L1 expression and infiltration by CD4+ and FoxP3+ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis

“…It can be caused by infiltrating immune cells producing factors driving PD‐L1 expression . Previous studies have also shown that TILs are correlated with higher expression levels of PD‐L1 expression in breast and lung cancers …”

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

“…Several studies evaluated PD‐L1 expression according to baseline clinicopathological features of patients with BC, consistently reporting a correlation between higher PD‐L1 expression and unfavorable classic prognostic factors, particularly poorer histological grade , higher proliferative index , more advanced N stage , larger tumor size , and younger age at BC diagnosis .…”

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

“…Several studies evaluate the importance of PD-1/PD-L1 expression on tumor cells and/or immune cells and the presence of TILs and Tregs in the tumor microenvironment in predicting response to treatment pertaining to BC [3,104,108,113,114]. Specifically, blocking immune evasion and attracting more TILs and fewer Tregs (reactivating immunogenicity of BC) to the tumor microenvironment can improve the OS of BC patients [19,23,[115][116][117][118][119]. Sixteen percent of HER2 + subtypes are lymphocyte predominant (> 50-60% of TILs present) and are associated with improved outcome (EFS: event-free survival, OS) with many treatment modalities [19,[120][121][122][123][124].…”

“…Moreover, based on 6 different studies, in [130], the authors highlight that PD-L1 expression in both tumor cells and immune cells of the host can contribute to the overall response to treatment. Hence, the evaluation of an overall expression in both these cells is recommended as a predictive biomarker [23,[115][116][117][118][119].…”