Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine.
Afshin DerakhshaniShahryar HashemzadehZahra AsadzadehMahdi Abdoli ShadbadFarnaz RasibonabHossein SafarpourVahid JafarlouAntonio Giovanni SolimandoVito RacanelliPankaj Kumar SinghSouzan NajafiDarya JavadrashidOronzo BrunettiNicola SilvestrisBehzad BaradaranPublished in: Cancers (2021)
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.
Keyphrases
- induced apoptosis
- cell cycle arrest
- poor prognosis
- cell death
- immune response
- gene expression
- endoplasmic reticulum stress
- long non coding rna
- randomized controlled trial
- binding protein
- squamous cell carcinoma
- oxidative stress
- end stage renal disease
- dendritic cells
- ejection fraction
- peritoneal dialysis
- open label
- rna seq
- metastatic colorectal cancer