Abstract
CD40 is an important tumor necrosis factor receptor (TNFR) family protein for the development of antitumor response against cancer cells, apart from its role in the regulation of the immune system as a costimulatory molecule. It is broadly expressed on the surface of immune cells and in diverse cancer types, including breast cancer. Here, we analyzed both CD40/CD40 ligand expression in breast cancer cells and tissues using public data sets and overall survival analysis in ungrouped breast cancer patients, as well as in the triple-negative breast cancer subtype. We detected CD40 gene expression along with its 3 different splice variants (variants 1–3), predominantly in the triple-negative subgroup of breast cancer cell lines. The results of the overall survival analysis showed that high CD40 gene expression, particularly in the triple-negative subgroup of breast cancer patients, is associated with better survival. In addition to the transcriptional levels of CD40 splice variants, investigation of protein levels of these variants will allow the categorization of breast cancer cells and reveal their potential as an immunotherapeutic target.
Highlights
CD40, a member of the tumor necrosis factor (TNF) family, is a 48 kDa Type I transmembrane glycoprotein
We showed the transcriptional variants of the CD40 gene in different breast cancer cell lines
High CD40 expression is associated with a good prognosis in breast cancer Prognostic value of CD40 gene expression was determined in breast cancer using the Kaplan–Meier plotter
Summary
CD40, a member of the tumor necrosis factor (TNF) family, is a 48 kDa Type I transmembrane glycoprotein. It is expressed on the surface of B cells, macrophages,and dendritic cells, as well as in various cancer cell lines and tissues including non-small cell lung cancer, ovarian, urinary bladder cancer, breast melanoma, pancreatic cancer, colon cancer, and B-lineage malignancies (Ara et al, 2018; Argiriadi et al, 2019; Piechutta and Berghoff, 2019). Agonistic antibodies against CD40 display T cell dependent antitumor activity, especially when used in combination with chemotherapy and immune checkpoint inhibitors (Bonaventura et al, 2019). It has been suggested that IL-2/CD40 or IL-15/CD40 combination therapy may be more effective than anti-CD40 alone for the advanced treatment of solid tumors, including renal cell carcinoma (Piechutta and Berghoff, 2019)
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