The ratio of CD4/CD8 T-cells in human papillomavirus-positive laryngeal squamous cell carcinoma accounts for improved outcome

Abstract

Conclusion: Improved prognosis associated with HPV-positive status may depend on lower CD4/CD8 ratio. Th1 CD4⁺T cells were found to be the major sub-set of T lymphocytes in the HPV positive laryngeal squamous cell carcinoma microenvironment. Background: To examine the prognostic significance of human papillomavirus (HPV) status in relation to the ratio of CD4/CD8 in LSCC. Methods: In this study, 46 LSCC biopsy samples were retrospectively assessed using immunohistochemistry for CD4⁺and CD8⁺tumor infiltrating lymphocytes (TILs). HPV status was determined by HPV in situ hybridization (ISH) and p16^INK4A immunohistochemistry. Of the 46 samples, 21 were evaluated for the expression of IFN-γ and IL-4 by quantitative real-time PCR (qRT-PCR). The influence of HPV status on locoregional tumor control and T-cell sub-sets infiltrating tumor microenvironment were investigated. Results: Nineteen patients (41.3%) were classified as HPV positive, who had improved disease-free survival (28% in reduction, hazard ratio =0.10; 95% CI =0.011–0.938). A direct correlation between the HPV status and the ratio of CD4/CD8 or mean levels of CD8⁺T cells was observed. Compared with the HPV-negative samples, HPV-positive samples had a higher ratio of IFN-γ/IL-4 (24.43 ± 29.89 vs 3.90 ± 4.03; p = 0.0375).

Keywords:

• HPV
• CD4/CD8
• LSCC
• TILs
• IFN-γ/IL-4

Acknowledgments

We thank the staff of Shanghai Institute of Immunology, Shanghai Jiaotong University, for their technical support and expertise. This work was sponsored by The National Natural Science Foundation of China (Grant number: 30972691, 30801283), The Technology Project of Shanghai (Grant number: 11JC1410802, 09QA1401000, 10QA1405900, 14411961900), Shanghai’s Health System of Talents Training Plan (Grant number: XYQ2011055, XYQ2011015).

The underlying research materials for this article can be accessed at Supplementary Figure 1:https://figshare.com/s/7c7258de4dc8c4532cda Supplementary Table 1:https://figshare.com/s/78069592ad4737cd852f Supplementary Table 2:https://figshare.com/s/3a30e194d5043b582688 Supplementary Table 3:https://figshare.com/s/3a78ad038964e9f39a2f

Disclosure statement

The authors report no conflicts of interest.