Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2022; 14(12): 2329-2339
Published online Dec 15, 2022. doi: 10.4251/wjgo.v14.i12.2329
Expression of nucleus accumbens-1 in colon cancer negatively modulates antitumor immunity
Zhao-Hua Shen, Wei-Wei Luo, Xing-Cong Ren, Xiao-Yan Wang, Jin-Ming Yang
Zhao-Hua Shen, Wei-Wei Luo, Xiao-Yan Wang, Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
Xing-Cong Ren, Jin-Ming Yang, Department of Cancer Biology and Toxicology, University of Kentucky College of Medicine, Lexington, MA 40506, United States
Author contributions: Yang JM and Wang XY supervised the project and revised the manuscript; Shen ZH performed the in vitro and in vivo experiments, generated the figures, and revised the manuscript; Luo WW completed the analysis of the results; Ren XC contributed to the study design.
Supported by the Changsha Municipal Natural Science Foundation, No. kq2014258.
Institutional review board statement: The study was reviewed and approved by the IRB of Third Xiangya Hospital, Central South University (Approval No. 2020-S195).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the IRB of Third Xiangya Hospital, Central South University (No. 2020-S298).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Data sharing statement: Data can be acquired from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jin-Ming Yang, Doctor, Academic Editor, Department of Cancer Biology and Toxicology, University of Kentucky College of Medicine, 101 Main Building Lexington, MA 40506, United States.
Received: July 10, 2022
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
Processing time: 154 Days and 24 Hours
Research background

Nucleus accumbens-1 (NAC-1) is highly expressed in a variety of tumors, and is closely associated with tumor recurrence, metastasis, and invasion.

Research motivation

We determined whether and how NAC-1 affects antitumor immunity in colon cancer.

Research objectives

To determine whether and how NAC-1 affects tumor microenvironment in colon cancer.

Research methods

NAC-1-siRNA, cytocidal test, quantitative real-time polymerase chain reaction, and Western blotting, a double luciferase reporter assay were used.

Research results

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.

Research conclusions

Tumor expression of NAC-1 is a negative determinant of immunotherapy.

Research perspectives

Our study suggests that targeting tumoral NAC-1 may be explored as a potential therapeutic strategy to enhance cancer immunotherapy.