Research Progress on the NF-κB Signaling Pathway and Tumor Microenvironment

Authors

  • Zihan Su

DOI:

https://doi.org/10.61173/yarqsy28

Keywords:

NF-κB signaling pathway, Immune evasion, Tumor microenvironment

Abstract

Cancers are major threats in the global health field with increased cases of occurrences. It progresses through several different steps, with all of them intricate chemical signaling. Recent progress in tumor microenvironment studies have revealed that tumors are robust communities that are constituted by tumor cells, immune cells and other stromal cells. The tumor immune microenvironment is central to the tumor microenvironment and has a fundamental influence on tumor progression and prognosis and directly on the effectiveness of anti-tumor therapy. In case the malfunction of immune cells occurs, that will result in dysfunction of the immune system, and it will be harder to treat. The NF-κB family of key transcription factors is one of the numerous signal transduction pathways involved in the tumor immune microenvironment and has received significant attention because of its involvement in the survival of cells, immunity, and inflammation. Canonical NF-κB is directly related to the progression of malignancies. Their state of functional activities and cytokine secretion can be fine-tuned by it to affect the malignant states of cancer cells and reconfigure the immune microenvironment of tumors. This writing guideline attempts to delve into the regulatory mechanism of the NF-κB pathway in the tumor microenvironment and the consequences in cancer therapy through immunotherapy. It also addresses the existing issues and gives suggestions about the clinical applications in the future.

References

[1] Vitale I, Manic G, Coussens L M, et al. Macrophages and Metabolism in the Tumor Microenvironment. Cell Metab, 2019, 30(1): 36-50.

[2] Fatima S. Tumor Microenvironment: A Complex Landscape of Cancer Development and Drug Resistance. Cureus, 2025, 17(4): e82090.

[3] Bejarano L, Jordāo M J C, Joyce J A. Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov, 2021, 11(4): 933-959.

[4] Cao Y, Yi Y, Han C, et al. NF-κB signaling pathway in tumor microenvironment. Front Immunol, 2024, 15: 1476030.

[5] Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol, 2009, 1(4): a000034.

[6] Lee K Y, Ito K, Hayashi R, et al. NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription. J Immunol, 2006, 176(1): 603-615.

[7] Antonangeli F, Natalini A, Garassino M C, et al. Regulation of PD-L1 Expression by NF-κB in Cancer. Front Immunol, 2020, 11: 584626.

[8] Korbecki J, Barczak K, Gutowska I, et al. CXCL1: Gene, Promoter, Regulation of Expression, mRNA Stability, Regulation of Activity in the Intercellular Space. Int J Mol Sci, 2022, 23(2).

[9] Flores R R, Clauson C L, Cho J, et al. Expansion of myeloidderived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism. Aging Cell, 2017, 16(3): 480-487.

[10] Parker K H, Sinha P, Horn L A, et al. HMGB1 enhances immune suppression by facilitating the differentiation and suppressive activity of myeloid-derived suppressor cells. Cancer Res, 2014, 74(20): 5723-5733.

[11] Kim N R, Kim Y J. Oxaliplatin regulates myeloidderived suppressor cell-mediated immunosuppression via downregulation of nuclear factor-κB signaling. Cancer Med, 2019, 8(1): 276-288.

[12] Porta C, Consonni F M, Morlacchi S, et al. Tumor- Derived Prostaglandin E2 Promotes p50 NF-κB-Dependent Differentiation of Monocytic MDSCs. Cancer Res, 2020, 80(13): 2874-2888.

[13] Richmond A, Yang J. The role of NF-kB in modulating antitumor immunity. Oncoimmunology, 2016, 5(1): e1005522.

[14] Barnes S E, Wang Y, Chen L, et al. T cell-NF-κB activation is required for tumor control in vivo. J Immunother Cancer, 2015, 3(1): 1.

[15] O’sullivan B J, Thomas R. CD40 ligation conditions dendritic cell antigen-presenting function through sustained activation of NF-kappaB. J Immunol, 2002, 168(11): 5491-5498.

Downloads

Published

2026-02-28