Immune checkpoints: Cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 in breast cancer surgery.

Abstract

Immune checkpoints refer to a plethora of inhibitory pathways built into the immune system, and recent studies have emphasized the role of these checkpoints in carcinogenesis. The aim of the present study was to evaluate two major immune checkpoints, the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), in the serum of 35 patients with stage I and II breast cancer. Serum concentrations of CTLA-4 and PD-1 were measured at three time points: i) Preoperatively; ii) during anesthesia following the harvesting of sentinel nodes (SNs); and iii) 24 h postoperatively. Control samples were obtained from 25 healthy, age-matched females. Assessment of CTLA-4 and PD-1 expression levels was conducted using flow cytometry. A statistically significant difference in PD-1 expression was identified between breast cancer patients preoperatively and healthy controls (26.31±11.87 vs. 12.72±8.15; P<0.0001). In addition, a statistically significant association was found between CTLA-4 and PD-1 levels prior to surgery (P=0.0084). In addition, CTLA-4 expression was associated with age (P=0.0453), with elevated levels of CTLA-4 detected in older breast cancer patients. Higher PD-1 expression levels were observed in T2 tumors compared with T1 tumors prior to surgery and intraoperatively; however, the differences were not statistically significant. Furthermore, a decrease in PD-1 levels was observed subsequent to harvesting SNs with metastasis, but not in SN-negative patients (P=0.05). A negative correlation was also observed between PD-1 expression and progesterone receptor (PR) status following surgery (P=0.024). These results provided a basis for further investigation of immune checkpoints in breast cancer. Breast cancer patients exhibit an altered profile of immune checkpoint markers, with higher concentrations of PD-1 observed in larger, PR-negative tumors.