A study published in the recent issue of the journal Cancer Immunology Research suggests that cannabidiol (CBD) may enhance the effectiveness of atezolizumab, a drug commonly used in treating triple-negative breast cancer (TNBC).
The study, which was published online ahead of print by the National Library of Medicine, highlights the potential for CBD to be used as an immune modulator, offering a new avenue for improving cancer treatments.
Triple-negative breast cancer is an aggressive form of cancer that often relies on cytotoxic therapies. Current treatments include the combination of atezolizumab, an immune checkpoint inhibitor (ICI), with chemotherapy. However, the effectiveness of this combination is limited for patients with low reactivity to atezolizumab, prompting researchers to explore alternative treatments that could enhance its efficacy.
The study shows that CBD, a component derived from cannabis, not only promotes apoptotic cell death in TNBC cells but also stimulates the cGAS-STING pathway, leading to the upregulation of PD-L1, a protein involved in immune system modulation. This pathway activation improves the reactivity of TNBC cells to atezolizumab, potentially increasing its effectiveness as part of cancer immunotherapy.
In both in vitro and in vivo experiments, researchers observed that combining CBD with anti-PD-L1 antibodies significantly enhanced the anti-cancer immune response. These findings suggest that CBD could play a role in future combinatorial cancer treatment strategies, particularly for patients with low response rates to current therapies.
The study’s full abstract can be found below:
The treatment of patients with triple negative breast cancer (TNBC) relies on cytotoxic therapy. Currently, atezolizumab and chemotherapy can be combined in patients with TNBC. However, this approach is not effective for all patients with low reactivity to atezolizumab. As there is a lack of alternative treatment options, new anti-cancer drugs are urgently needed to enhance atezolizumab reactivity against TNBC. Recent strategies have focused on regulating the expression of programmed death-ligand 1 (PD-L1) or enhancing immune response activation by combining anti-cancer drugs with immune checkpoint inhibitors (ICIs). Cannabidiol (CBD), a cannabinoid component derived from the cannabis plant, has been reported to have anti-cancer therapeutic potential because of its capacity to induce apoptotic cell death in tumor cells while avoiding cytotoxicity in normal cells. Previous studies have demonstrated the effects of CBD on apoptosis in various cancer cell types. However, the potential role of CBD as an immune modulator in the regulation of PD-L1 expression and anti-cancer immune responses remains to be explored. In this study, we found that CBD stimulated PD-L1 expression in TNBC cells, which significantly induced the CBD-mediated cGAS-STING pathway activation. Taken together, we demonstrated that the combination of CBD and anti-PD-L1 antibody enhances the anti-cancer immune response in vitro and in vivo experiments. Our findings identified the mechanism of PD-L1 regulation by CBD in TNBC cells and suggested that CBD could be a potential candidate for the development of new combinatorial strategies with ICIs in TNBC patients.
