Skip to main content

Advertisement

Log in

Deregulation of cytokine affecting oral neutrophil subsets in oral cancer

  • Short Communication
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The most prevalent form of leukocytes in human blood, neutrophils, is regarded as an essential part of the innate immune system and the body’s 1st line of defense against foreign invaders. However, divergent opinions arise on the role of neutrophils in cancer, likely due to the occurrence of many neutrophil subsets. Several factors in the tumor microenvironment were found to modify the phenotype and function of neutrophils. Inhibitory cytokine production and recruitment of protumor immune cells to the tumor microenvironment are the reasons for immune suppression. Although some salivary cytokines were found to be increased in cancer patient’s saliva, simultaneously, it was observed that those cytokines are high in other oral inflammatory conditions. So, it is challenging to distinguish at what level of expression those cytokines are involved in the neoplastic process. Therefore, the goal of this study is to provide a summary of the current information about the existence and presence of specific cytokines that impact cPMN and TAN and their potential activities in the context of healthy and cancer states so that we can relate to oPMN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Data availability

Data was collected from Scopus, PubMed and goggle scholar.

Abbreviations

cPMN:

Circulating polymorphonuclear neutrophils

oPMN:

Oral polymorphonuclear neutrophils

IL:

Interleukin

TME:

Tumor microenvironment

TANs:

Tumor associated neutrophils

HDN:

High-density neutrophils

LDN:

Low-density neutrophils

TNF:

Tumor Necrosis Factor

References

  1. Berra A, et al. Role of salivary IgA in the pathogenesis of Sjögren syndrome. Clin Immunol. 2002;104(1):49–57.

    Article  CAS  PubMed  Google Scholar 

  2. Scully C. HIV topic update: salivary testing for antibodies. Oral Dis. 1997;3(4):212–5.

    Article  CAS  PubMed  Google Scholar 

  3. Bello PY, et al. Assessment of a hepatitis C virus antibody assay in saliva for epidemiological studies. Eur J Clin Microbiol Infect Dis. 1998;17(8):570–2.

    Article  CAS  PubMed  Google Scholar 

  4. Kaufman E, Lamster IB. The diagnostic applications of saliva–a review. Crit Rev Oral Biol Med. 2002;13(2):197–212.

    Article  PubMed  Google Scholar 

  5. Ferrari E, Pezzi ME, Cassi D, Pertinhez TA, Spisni A, Meleti M. Salivary cytokines as biomarkers for oral squamous cell carcinoma: a systematic review. Int J Mol Sci. 2021;22(13):6795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lenka S, Bhola RK, Varanasi PR, Bhuyan SK, Bhuyan R. Understanding the functional relevance of oral neutrophils, phenotype and properties in OSCC. Med Oncol. 2023;40(5):134.

    Article  CAS  PubMed  Google Scholar 

  7. Garley M, Jabłońska E. Heterogeneity among neutrophils. Arch Immunol Ther Exp (Warsz). 2018;66(1):21–30.

    Article  CAS  PubMed  Google Scholar 

  8. Fridlender ZG, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16(3):183–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Peng H, Shen J, Long X, Zhou X, Zhang J, Xu X, Huang T, Xu H, Sun S, Li C, Lei P. Local release of TGF-β inhibitor modulates tumor-associated neutrophils and enhances pancreatic cancer response to combined irreversible electroporation and immunotherapy. Adv Sci. 2022;9(10):e2105240.

    Article  Google Scholar 

  10. Korostoff A, et al. The role of salivary cytokine biomarkers in tongue cancer invasion and mortality. Oral Oncol. 2011;47(4):282–7.

    Article  CAS  PubMed  Google Scholar 

  11. Chen Z, et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res. 1999;5(6):1369–79.

    CAS  PubMed  Google Scholar 

  12. Roi A, Roi CI, Negruțiu ML, Riviș M, Sinescu C, Rusu LC. The challenges of OSCC diagnosis: salivary cytokines as potential biomarkers. J Clin Med. 2020;9(9):2866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Brailo V, et al. Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer. Med Oral Patol Oral Cir Bucal. 2012;17(1):e10–5.

    Article  PubMed  Google Scholar 

  14. Rhodus NL, et al. The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog. 2005;44(2):77–82.

    Article  CAS  PubMed  Google Scholar 

  15. Lee LT, et al. Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018;47(6):699–707.

    Article  CAS  PubMed  Google Scholar 

  16. Katakura A, et al. Comparison of salivary cytokine levels in oral cancer patients and healthy subjects. Bull Tokyo Dent Coll. 2007;48(4):199–203.

    Article  CAS  PubMed  Google Scholar 

  17. Sahibzada HA, et al. Salivary IL-8, IL-6 and TNF-α as potential diagnostic biomarkers for oral cancer. Diagnostics (Basel). 2017;7(2):21.

    Article  PubMed  Google Scholar 

  18. Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity. 2019;51(1):27–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jackson MW, et al. A potential autocrine role for vascular endothelial growth factor in prostate cancer. Cancer Res. 2002;62(3):854–9.

    CAS  PubMed  Google Scholar 

  20. Huakan Zhao LW. Guifang Yan, Yu Chen, Mingyue Zhou, Yongzhong Wu & Yongsheng Li Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther. 2021;6(1):263.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Prasad G, McCullough M. Chemokines and cytokines as salivary biomarkers for the early diagnosis of oral cancer. Int J Dent. 2013;2013:813756.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yan B, et al. IL-6 cooperates with G-CSF to induce protumor function of neutrophils in bone marrow by enhancing STAT3 activation. J Immunol. 2013;190(11):5882–93.

    Article  CAS  PubMed  Google Scholar 

  23. Huh SJ, et al. Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res. 2010;70(14):6071–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qin F, et al. Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer. J Cancer. 2020;11(9):2580–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sagiv JY, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015;10(4):562–73.

    Article  CAS  PubMed  Google Scholar 

  26. Shrivastava R, et al. M2 polarization of macrophages by Oncostatin M in hypoxic tumor microenvironment is mediated by mTORC2 and promotes tumor growth and metastasis. Cytokine. 2019;118:130–43.

    Article  CAS  PubMed  Google Scholar 

  27. Spicer JD, et al. Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 2012;72(16):3919–27.

    Article  CAS  PubMed  Google Scholar 

  28. Lakschevitz FS, Aboodi GM, Glogauer M. Oral neutrophil transcriptome changes result in a pro-survival phenotype in periodontal diseases. PLoS ONE. 2013;8(7):e68983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Novak T, Fortune F, Bergmeier L, Khan I, Hagi-Pavli E. Neutrophil elastase and endogenous inhibitors in Behcet’s disease saliva. Clin Exp Immunol. 2020;202(1):93–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Girard D, Paquin R, Beaulieu AD. Responsiveness of human neutrophils to interleukin-4: induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis. Biochem J. 1997;325(Pt 1):147–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li B, Liu Y, Hu T, Zhang Y, Zhang C, Li T, Wang C, Dong Z, Novakovic VA, Hu T, Shi J. Neutrophil extracellular traps enhance procoagulant activity in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2019;1(145):1695–707.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to express their gratitude to the president of Siksha 'O' Anusandhan (deemed to be university), India for giving the required facilities to carry out the aforementioned study.

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

SL performed literature searches and wrote the manuscript. SKB reviewed the manuscript. SB edited and designed the manuscript. All authors contributed to manuscript revision, and approved the submitted version.

Corresponding author

Correspondence to Ruchi Bhuyan.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lenka, S., Bhuyan, S.K. & Bhuyan, R. Deregulation of cytokine affecting oral neutrophil subsets in oral cancer. Med Oncol 40, 307 (2023). https://doi.org/10.1007/s12032-023-02190-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-023-02190-8

Keywords

Navigation