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. 2021 Jan-Mar;62(1):249-253.
doi: 10.47162/RJME.62.1.25.

CD4+ CD25+ regulatory T-cells role in tumor microenvironment of the squamous cell carcinoma

Affiliations

CD4+ CD25+ regulatory T-cells role in tumor microenvironment of the squamous cell carcinoma

Andrei Vasile Paşcalău et al. Rom J Morphol Embryol. 2021 Jan-Mar.

Abstract

Introduction: Squamous cell carcinoma (SCC) is the most common skin cancer with a high rate of death. Different lymphocyte populations play an important role in modulating the immune response in the tumor microenvironment. The increase in the proportion of cluster of differentiation (CD)4+ CD25+ regulatory T-cell (Treg) lymphocytes is associated, in different studies, with the increase of the cell multiplication rate.

Aim: To analyze the Treg lymphocyte subpopulations and to correlate the results with the presence of the CD8+ cytotoxic T-cell (Tc) lymphocyte population.

Materials and methods: Sixty primary skin SCC specimens were incubated with anti-CD8 (clone SP57) rabbit monoclonal antibody and anti-CD25 (clone 4C9) mouse monoclonal antibody.

Results: The ratio of the intratumoral∕peritumoral CD4+ CD25+ forkhead box protein p3 (Foxp3) lymphocytes was 0.46, emphasizing that at tumor margins, where tumor aggressiveness is higher, these lymphocytes subpopulations facilitate tumor progression. The comparative analysis of the tumor microenvironment profile revealed that in the case of intratumoral immune response, the number of Tc-type lymphocytes (CD8+) was 3.34 times higher compared to Treg lymphocytes (p<0001). In the peritumoral area, the number of Tc lymphocytes was 5.05 times higher compared to Treg lymphocytes (p<0001).

Conclusions: Treg lymphocytes inhibition may cause the suppression of the antitumoral cell immune response in the tumor environment. We believe that Treg lymphocytes should represent a focus of interest for a new personalized therapy. New studies are needed to better understand the immune response in the tumor microenvironment.

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Conflict of interest statement

The authors declare that they have no conflict of interests. All authors read and approved the final manuscript.

Figures

Figure 1
Figure 1
The distribution cases curve graph of the immune profile. Foxp3: Forkhead box protein p3; Tc: Cytotoxic T-cell
Figure 2
Figure 2
Low number of Treg lymphocytes (brown) in the tumor bed of squamous cell carcinoma (100×). Treg: Regulatory T-cell
Figure 3
Figure 3
Islands of squamous cell carcinoma that have at the periphery a limited number of Treg lymphocytes (brown) compared to other subclasses of lymphocytes (100×). Treg: Regulatory T-cell
Figure 4
Figure 4
Two islands of squamous cell carcinoma including diffuse infiltration of Treg lymphocytes (100×). Treg: Regulatory T-cell
Figure 5
Figure 5
On the right side, there is a tumor bed and at the level of the contact interface, there is a high number of Treg lymphocytes (brown) (100×). Treg: Regulatory T-cell
Figure 6
Figure 6
The comparative analysis of the tumor microenvironment immune profile. Tc: Cytotoxic T-cell

References

    1. Yan W, Wistuba II, Emmert-Buck MR, Erickson HS. Squamous cell carcinoma - similarities and differences among anatomical sites. Am J Cancer Res. 2011;1(3):275–300. - PMC - PubMed
    1. Rahimi S. Squamous cell carcinoma of skin: a brief review. Clin Ter. 2013;164(2):143–147. - PubMed
    1. Dotto GP, Rustgi AK. Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell. 2016;29(5):622–637. - PMC - PubMed
    1. Oliveira-Neto HH, Leite AF, Costa NL, Alencar RC, Lara VS, Silva TA, Leles CR, Mendonça FE, Batista AC. Decrease in mast cells in oral squamous cell carcinoma: possible failure in the migration of these cells. Oral Oncol. 2007;43(5):484–490. - PubMed
    1. Akbar AN, Taams LS, Salmon M, Vukmanovic-Stejic M. The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology. 2003;109(3):319–325. - PMC - PubMed

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