Breast cancer (BC) is not only a mass of malignant cells but also a systemic inflammatory disease. BC pro-tumorigenic
inflammation has been shown to promote immune evasion and provoke BC progression. The
NOD-like receptor (NLR) family pyrin domain-containing
protein 3 (NLRP3)
inflammasome is activated when
pattern recognition receptors (
PRRs) sense danger signals such as
calreticulin (CALR) from damaged/dying cells, leading to the secretion of interleukin-1β (IL-1β). CALR is a novel BC
biological marker, and its high levels are associated with advanced
tumors. NLRP3 expression is strongly correlated with an elevated proliferative index Ki67, BC progression,
metastasis, and recurrence in patients with
hormone receptor-positive (HR+) and triple-negative BC (TNBC). Tumor-associated macrophages (TAMs) secrete high levels of IL-1β promoting endocrine resistance in HR+ BC. Recently, an immunosuppressive soluble form of
programmed death ligand 1 (sPD-L1) has been identified as a novel prognostic
biomarker in
triple-negative breast cancer (TNBC) patients. Interestingly, IL-1β induces sPD-L1 release. BC Patients with elevated IL-1β and sPD-L1 levels show significantly short progression-free survival. For the first time, this study aims to investigate the inhibitory impact of
thymoquinone (TQ) on CALR, the NLRP3 pathway and sPD-L1 in HR+ and TNBC. Blood samples were collected from 45 patients with BC. The effect of differing TQ concentrations for different durations on the expression of CALR, NLRP3 complex components and IL-1β as well as the
protein levels of sPD-L1 and IL-1β were investigated in the peripheral blood mononuclear cells (PBMCs) and TAMs of TNBC and HR+ BC patients, respectively. The findings showed that TQ significantly downregulated the expression of CALR, NLRP3 components and IL-1β together with the
protein levels of secreted IL-1β and sPD-L1. The current findings demonstrated novel immunomodulatory effects of TQ, highlighting its potential role not only as an excellent adjuvant but also as a possible immunotherapeutic agent in HR+ and TNBC patients.