Published online Dec 15, 2022. doi: 10.4251/wjgo.v14.i12.2329
Peer-review started: July 10, 2022
First decision: September 26, 2022
Revised: October 16, 2022
Accepted: November 21, 2022
Article in press: November 21, 2022
Published online: December 15, 2022
Nucleus accumbens-1 (NAC-1) is highly expressed in a variety of tumors, inclu
To determine whether and how NAC-1 affects antitumor immunity in colon cancer.
NAC-1-siRNA was transfected into RKO colon cancer cells to knock down NAC expression; tumor cells with or without knockdown of NAC-1 were treated with CD8+ T cells to test their cytocidal effect. The level of the immune checkpoint programmed death receptor-1 ligand (PD-L1) in colon cancer cells with or without knockdown of NAC-1 was analyzed using Quantitative real-time poly
Knockdown of NAC-1 expression in colon cancer cells significantly enhanced the cytocidal effect of CD8+ T cells in cell culture experiments. The sensitizing effect of NAC-1 knockdown on the antitumor action of cytotoxic CD8+ T cells was recapitulated in a colon cancer xenograft animal model. Furthermore, knockdown of NAC-1 in colon cancer cells decreased the expression of PD-L1 at both the mRNA and protein levels, and this effect could be rescued by transfection of an RNAi-resistant NAC-1 expression plasmid. In a reporter gene assay, transient expression of NAC-1 in colon cancer cells increased the promoter activity of PD-L1, indicating that NAC-1 regulates PD-L1 expression at the transcriptional level. In addition, depletion of tumoral NAC-1 increased the number of CD8+ T cells but decreased the number of suppressive myeloid-derived suppressor cells and regulatory T cells.
Tumor expression of NAC-1 is a negative determinant of immunotherapy.
Core Tip: We determined whether and how nucleus accumbens-1 (NAC-1) affects antitumor immunity in colon cancer. Knockdown of NAC-1 expression in colon cancer cells significantly enhanced the cytocidal effect of CD8+ T cells. Knockdown of NAC-1 in colon cancer cells decreased the expression of progra