Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck

Abstract

Background: A crucial role for the immune system has been proposed in the establishment and progression of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the cytokine and regulatory profiles of T cells in tumor draining lymph nodes (TDLNs) of patients with HNSCC.

Results: The frequencies of CD4⁺TNF-α⁺ and CD4⁺TNF-α^hi negatively were associated with poor prognostic factors such as LN involvement (P = 0.015 and P = 0.019, respectively), stage of the disease (P = 0.032 and P = 0.010, respectively) and tumor size (P = 0.026 and P = 0.032, respectively). Frequencies of CD8⁺IFN-γ⁺ and CD8⁺IFN-γ⁺ TNF-α⁺ T cells showed negative relationship with tumor grade (P = 0.035 and P = 0.043, respectively). While, the frequencies of CD4⁺IL-4⁺, CD8⁺IL-10⁺, CD8⁺IL-4⁺T cells were higher in advanced stages of the disease (P = 0.042, P = 0.041 and P = 0.030, respectively) and CD4⁺IFN-γ⁺TNF-α^-, CD8⁺IL-4⁺ and CD8⁺IFN-γ⁺TNF-α^- T cells were higher in patients with larger tumor size (P = 0.026 and P = 0.032, respectively). Negative associations were found between the frequencies of CD4⁺CD25⁺Foxp3⁺ and CD4⁺CD25⁺Foxp3⁺CD127^low/- Treg cells and cancer stage (P = 0.015 and P = 0.059).

Conclusion: This study shed more lights on the changes in immune profile of T cells in TDLNs of HNSCC. Larger tumor size and/or LN involvement were associated with lower frequencies of CD4⁺TNF-α⁺, CD8⁺IFN-γ⁺ and CD8⁺IFN-γ⁺TNF-α⁺ but higher frequency of CD4⁺IL-4⁺ T cells. Moreover, Foxp3⁺Tregs correlated with good prognostic indicators.

Keywords: Cytokine profile; Head and neck squamous cell carcinoma; Immune profile; Regulatory T cells; T lymphocytes; Tumor draining lymph nodes.