Open Access

Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC

  • Authors:
    • Yang Yang
    • Xiaoli Zheng
    • Peizan Ni
    • Dingjie Li
    • Qinfu Dan
    • Xiaohui Wang
    • Yunhan Wang
    • Yanan Sun
    • Kangdong Liu
    • Zigang Dong
    • Hong Ge
  • View Affiliations

  • Published online on: November 25, 2022     https://doi.org/10.3892/ijo.2022.5460
  • Article Number: 12
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As a metabolic mediator of antitumor immunity, indoleamine‑2,3‑dioxygenase 1 (IDO1) is upregulated in various types of cancer; however, the regulatory mechanism and clinical significance of IDO1 in non‑small cell lung cancer (NSCLC) radiotherapy (RT) remain unclear. The present study investigated the role of IDO1 in the NSCLC microenvironment. MTT assay, immunofluorescence, apoptosis analysis, cell cycle analysis, and C57BL/6 and BALB/c nude mouse tumor models were utilized to evaluate the roles of the STAT5A/IDO1/kynurenine axis in radioresistance and in the immune microenvironment of NSCLC. Protein expression levels were evaluated by western blotting, immunofluorescence and immunohistochemistry. Flow cytometry was performed to assess the status of CD8+ T lymphocytes, regulatory T cells (Tregs) and immune‑related inflammatory factors in C57BL/6 mice. Notably, IDO1 and STAT5A were positively associated with the immune microenvironment. RT treatment significantly promoted the expression levels of IDO1. IDO1 knockdown markedly enhanced the radiosensitivity of lung tumor cells and the anti‑apoptotic properties of T lymphocytes. It was demonstrated that STAT5A knockdown suppressed T‑cell apoptosis by inhibiting IDO1 enzyme function. Finally, in vivo experiments showed that STAT5A knockdown combined with RT was associated with greater numbers of CD8+ T cells and fewer Tregs. Results from the present study indicated that targeting the STAT5A/IDO1 axis may reshape the immune microenvironment and promote the efficacy of RT in NSCLC treatment. The present study may provide a theoretical foundation for more efficient use of immunotherapy regimens in NSCLC treatment.
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January-2023
Volume 62 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yang Y, Zheng X, Ni P, Li D, Dan Q, Wang X, Wang Y, Sun Y, Liu K, Dong Z, Dong Z, et al: Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC. Int J Oncol 62: 12, 2023
APA
Yang, Y., Zheng, X., Ni, P., Li, D., Dan, Q., Wang, X. ... Ge, H. (2023). Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC. International Journal of Oncology, 62, 12. https://doi.org/10.3892/ijo.2022.5460
MLA
Yang, Y., Zheng, X., Ni, P., Li, D., Dan, Q., Wang, X., Wang, Y., Sun, Y., Liu, K., Dong, Z., Ge, H."Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC". International Journal of Oncology 62.1 (2023): 12.
Chicago
Yang, Y., Zheng, X., Ni, P., Li, D., Dan, Q., Wang, X., Wang, Y., Sun, Y., Liu, K., Dong, Z., Ge, H."Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC". International Journal of Oncology 62, no. 1 (2023): 12. https://doi.org/10.3892/ijo.2022.5460