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

Research output: Contribution to journalArticlepeer-review


BACKGROUND Nucleus accumbens-1 (NAC-1) is highly expressed in a variety of tumors, including colon cancer, and is closely associated with tumor recurrence, metastasis, and invasion. AIM To determine whether and how NAC-1 affects antitumor immunity in colon cancer. METHODS 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 polymerase chain reaction and Western blotting. A double luciferase reporter assay was used to examine the effects of NAC-1 on the transcription of PD-L1. Mice bearing MC-38-OVA colon cancer cells expressing NAC-shRNA or controlshRNA were treated with OT-I mouse CD8+ T cells to determine the tumor response to immunotherapy. Immune cells in the tumor tissues were analyzed using flow cytometry. NAC-1, PD-L1 and CD8+ T cells in colon cancer specimens from patients were examined using immunohistochemistry staining. 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 recapit ulated 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. CONCLUSION Tumor expression of NAC-1 is a negative determinant of immunotherapy.

Original languageEnglish
Pages (from-to)2329-2339
Number of pages11
JournalWorld Journal of Gastrointestinal Oncology
Issue number12
StatePublished - Dec 15 2022

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.


  • Cd8+t cells
  • Colon cancer
  • Nucleus accumbens-1
  • Programmed death receptor-1/programmed death receptor-1 ligand
  • Tumor immunity

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology


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