Intracellular CTLA4 and Regulatory T Cells in Patients with Laryngeal Squamous Cell Carcinoma

Abstract

To explore if the increased percentages of Regulatory T (Treg) cells, as well as, overexpression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) are involved in laryngeal-squamous cell carcinoma (SCC), 45 patients with laryngeal-SCC and 27 healthy controls were enrolled. Flow cytometry was performed to investigate, in the peripheral blood, the prevalence of CD4+CD25+FoxP3+ Treg cells, as well as, surface and intracellular expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). The results indicated intracellular (In)CTLA4 with considerable higher expression in the CD8+ lymphocytes among patients with laryngeal-SCC compared with the control group (8.2 ± 8.7 versus 2.3 ± 3.5, P = 0.001). The mean percentage of InCTLA4+CD4+ and InCTLA4+CD19+ lymphocytes was also significantly higher in patients (8.7 ± 7.8 versus 4.4 ± 4.2, P = 0.018 and 0.6 ± 0.8 versus 0.2 ± 0.2, P = 0.024, respectively). With respect to surface (Sur)CTLA4, the difference between patients and controls was, however, significant only in the case of CD8+ lymphocytes (0.7 ± 0.6 versus 0.3 ± 0.3, P = 0.003, respectively). The percentage of Treg cells was observed to be significantly higher in patients (7.5 ± 6.3 and 3.2 ± 1.9, P < 0.0001). Furthermore, association analysis revealed the association of Treg cell increase with the higher tumor-size and lymphnode stage (P < 0.005). These data collectively suggest that patients with laryngeal-SCC may benefit from immunotherapy targeting CTLA4 and Treg cells.

• Tumor immunology
• Regulatory T cells
• Head and Neck cancer
• Laryngeal squamous cell carcinoma (SCC)
• CTLA-4
• FoxP3

ACKNOWLEDGMENT

This study was financially supported by a grant from Shiraz University of Medical Sciences (Grant No. 87-4439) and also a grant from Shiraz Institute for Cancer Research. The project had been submitted as the MD thesis project of Dr. Behzad Khademi at Shiraz University of Medical Sciences. The authors would like to acknowledge Dr. Peyman Jafari for his assistance in the statistical analyses.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.