The influence of immune checkpoint inhibitors on anti-tumor immunity in head and neck cancer

Immune evasion is an important mechanism that can lead to uncontrolled proliferation and metastasis of tumor cells. Natural control mechanisms such as immune checkpoints are used to weaken an anti-tumor immune response. Blocking these inhibitory signaling pathways with checkpoint inhibitors (CI) already shows positive effects in cancer therapy.

The influence of checkpoint inhibitors such as PD-1, CTLA4 and BTLA4 on Cancer Testis Antigen (CTA) and Tumor Associated Antigen (TAA) -specific T cells is determined by a mixed lymphocyte-peptide culture and EliSpot assays with regard to cytokine secretion and investigated cytotoxicity against HNSCC tumor cell lines. In addition, a potential effect of the inhibitor treatment on the expression of various checkpoint molecules will be analyzed using flow cytometry.

Treatment with various checkpoint inhibitors (CI) induced a significantly increased interferon-γ secretion in CTA- and TAA-specific immune cells. In addition, there was an increased cytotoxicity of the CI-treated specific T cells with increased granzyme B secretion in co-culture with HNSCC tumor cell lines. In addition, the expression pattern of various checkpoint molecules on the surface of the lymphocytes changed after treatment with the PD1 inhibitor nivolumab, in vitro.

The anti-tumor immune response of CTA- and TAA-specific immune cells can be increased by the administration of various immune checkpoint inhibitors and increases tumor-directed cytotoxicity. These in vitro tests suggest that a combination of checkpoint inhibitors and peptide therapies against TAA such as MAGE-A3 or NY-ESO-1 could achieve better therapeutic success than monotherapy.

 

MissingLinkText

Conflict of Interest

The author declares that there is no conflict of interest.

Publication History

Article published online:
24 May 2022