Immune Checkpoint expression on lymphocyte subsets may depend on HLA-Type of patients with head neck squamous cell carcinoma (HNSCC)

Introduction:

Inhibitory immune checkpoints like „Cytotoxic T-Lymphocyte Antigen 4“ (CTLA4) and „Programmed Cell Death-1“ (PD-1) are important targets for immunotherapy. However, T-cell activation requires antigen presentation by Human-Leukocyte-Antigens (HLA). Because of the peptide restriction of HLA-class I molecules the presented antigens are dependent on the HLA genotype. Therefore, the expression of inhibitory checkpoints may differ depending on the HLA-type. The aim of this study was to analyze immune checkpoint expression on different lymphocyte subsets in association with HLA factors.

Methods:

Within prospective, non-interventional studies, 42 HNSCC patients were HLA-typed by next generation sequencing. Immune checkpoint expression was analyzed with flow cytometry. Based on the findings published by Wichman et al. patients were grouped by HLA-alleles with positive and negative impact on progression free survival (PFS). Immune checkpoint expression in various lymphocyte subsets were then compared for the two HLA-predictor groups.

Result:

Our data showed a significantly increased CTLA4-expression on CD4- and CD8-positive T cells as well as CD39-positive regulatory T cells in patients with predominantly positive prognostic HLA alleles compared to those with predominantly negative HLA-alleles.

Conclusion:

The increased CTLA4-expression on lymphocytes among patients with good prognosis HLA-types could be a hint for the presence of suppressed cancer immunity. Identification of the presented antigens and further confirmatory functional tests are needed.

Publication History

Publication Date:
23 April 2019 (online)