Abstract
Triple negative breast carcinoma (TNBC) is a rapid progressive tumor and has a poor overall survival. Therefore, it is crucial to find out effective molecular targets and develop optimal therapeutic strategies for TNBC. In this study, immunohistochemical staining was used to detect expressions of programmed death-ligand 1 (PD-L1) and phosphatase and tensin homolog (PTEN) in 136 breast carcinomas including 50 TNBC. The effect of PTEN on regulation of PD-L1 expression was assessed in vitro in the PTEN knockdown TNBC cells. We found that PD-L1(SP142) positive rate in TNBC (48.0%) was significantly higher than non-TNBC (23.3%). PTEN negative rate was 42% in TNBC. The inverse correlation between PTEN and PD-L1(SP142) expression in TNBC was statistically significant (P<0.05). After PTEN knockdown, PD-L1 expression in TNBC cells increased significantly, and the expression level of AKT increased simultaneously. PTEN knockdown promoted cell proliferation, viability and G1/S switch of TNBC cells. These results suggested that PTEN may involve in regulation of PD-L1 expression, because PTEN loss can upregulate PD-L1 expression in TNBC. Antitumor immunity of PD-L1 could be enhanced in TNBC when targeting PTEN at the same time.
Highlights
Triple negative breast carcinoma (TNBC) is characterized by lacking of expression of estrogen receptor (ER), progesterone receptor (PR) and gene amplification of human epidermal growth factor receptor type 2 (HER2), namely, it lacks corresponding therapeutic targets of endocrine and HER2[1]
We found that programmed death-ligand 1 (PD-L1)(SP142) positive rate in TNBC (48.0%) was significantly higher than non-TNBC (23.3%)
phosphatase and tensin homolog (PTEN) knockdown promoted cell proliferation, viability and G1/S switch of TNBC cells. These results suggested that PTEN may involve in regulation of PD-L1 expression, because PTEN loss can upregulate PD-L1 expression in TNBC
Summary
Triple negative breast carcinoma (TNBC) is characterized by lacking of expression of estrogen receptor (ER), progesterone receptor (PR) and gene amplification of human epidermal growth factor receptor type 2 (HER2), namely, it lacks corresponding therapeutic targets of endocrine and HER2[1]. PD-L1 expressed by tumor cells down regulates immune responses through binding to its two receptors programmed death-1 (PD-1) and B7.1. PD-L1 binding to PD-1 and B7.1 on T cells and antigen presenting cells can mediate down-regulation of immune responses, including inhibition of T-cell activation and cytokine production, resulting in an immune evasion[3, 4]. Treated with the PD-L1 antibody avelumab the patients with metastatic TNBC showed better outcomes with a 31% disease control rate[8]. These data suggest that immunotherapy using PD-L1 antibodies is an encouraging efficacy way for patients with TNBC. PTEN loss is correlated with ER/PR negative and PI3K pathway activation in breast cancers[12]. Our results demonstrate that PTEN is involved in regulation of PD-L1 expression in TNBC
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