Differential expression of Helios, Neuropilin-1 and FoxP3 in head and neck squamous cell carcinoma (HNSCC) patients
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In recent years, studies have begun to explore the immune involvement in head and neck tumors. Advanced stage head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with low survival rates with high level of immune infiltrates. Tregs (regulatory T cells) play a crucial role in constructing an immunosuppressive tumor microenvironment. In the present study, we highlighted specific Treg markers and its factors in HNSCC solid tumors and peripheral blood of cancer patients. By histopathology and immunofluorescence staining, we observed differential expression of CD4, CD25, Foxp3, Helios and Neuropilin-1. Further, we analyzed the expression of Foxp3, Helios, Neuropilin-1 and GARP by qPCR and flow cytometry in whole blood and found to be elevated in HNSCC patients in comparison with healthy donors. Additionally, IFN-γ, TGF-β, IL-6, IL-2, IL-10 and TNF-α expressions were also found to be relatively increased in the head and neck cancer patients when compared with healthy donors. Our findings emphasize that Tregs may be involved in promoting tumor progression. Helios and Neuropilin-1 could be potent markers in identifying subsets of Tregs. Association of soluble factors could sculpture the activity of Tregs. With further research, Treg markers and its associated soluble factors could be employed to block Tregs trafficking to the tumor, thus enlightening a potential strategy for targeting human cancers.
KeywordsSquamous cell carcinoma HNSCCs Tregs Foxp3 CD4 Soluble factors
We would like to thank DST-SERB (No: YSS/2014/000424) Govt. of INDIA and the first author thanks the Maulana Azad national fellowship scheme (UGC) (F1-17.1/2014-15/MANF-2014-15-MUS-PON-44115).
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to declare.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 68:394-424. doi:10.3322/caac.21492Google Scholar
- Drennan S, Stafford ND, Greenman J, Green VL (2013) Increased frequency and suppressive activity of CD127(low/−) regulatory T cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement. Immunology 140:335–343. https://doi.org/10.1111/imm.12144 CrossRefPubMedPubMedCentralGoogle Scholar
- Karagöz B et al. (2010) CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients Med Oncol 27:29-33 doi:10.1007/s12032-008-9165-9Google Scholar
- Kulkarni MR (2018) Head and neck cancer burden in india. Int J Head Neck Surg 10:10001–11132Google Scholar
- Mohamed Adil AA, Jamal S, Ahmed V (2014) Cancer immunotherapy: targeting immunosuppressive tumor microenvironment Oncobiology and Targets. Oncobiol Targets 1(27):1236Google Scholar
- Mohamed Adil AA, Anandraj V, Kumar S, Waseem M, Chitra K, Kumar BA, Jamal S, Ahmed N (2018) Role of mesenchymal cells and immunosuppressive cells within inflammatory tumor microenvironment. J Hematol Oncol Forcast 1:1005Google Scholar
- Phé V, Rouprêt M, Cussenot O, Chartier-Kastler E, Gamé X, Compérat E (2015) Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients. BJU Int 115:28–32. https://doi.org/10.1111/bju.13044 CrossRefPubMedGoogle Scholar
- Szurek E, Cebula A, Wojciech L, Pietrzak M, Rempala G, Kisielow P, Ignatowicz L (2015) Differences in expression level of Helios and Neuropilin-1 do not distinguish thymus-derived from extrathymically-induced CD4+Foxp3+ regulatory T cells. PLOS ONE 10:e0141161. https://doi.org/10.1371/journal.pone.0141161 CrossRefPubMedPubMedCentralGoogle Scholar
- Thornton AM, Korty PE, Kim YC, Martens C, Shevach EM (2018) Helios expression defines a phenotypically distinct population of Treg cells. J Immunol 200:116119–116119Google Scholar