Immune checkpoint inhibition increases antigen-specific T cell response in head and neck cancer

Abstract

Abstract Therapeutic strategies which target immune checkpoint markers and enable the immune system to initiate immune responses against tumor cells represent a major advancement in cancer therapy. The response rate to anti-PD-1 checkpoint inhibition in head and neck cancer is about 20%, which underlines the importance of finding further immune-based treatment options. Furthermore, the effects of immune checkpoint inhibitors on antigen-specific T cells have not yet been sufficiently explored, therefore more detailed investigations are required. In mixed lymphocyte-peptide cultures, specific cytotoxic T cells were generated against various tumor-associated antigens. Several tumor-associated antigens such as MAGE, PRAME and NY-ESO-1 were identified as the most potent immunostimulatory agents. The immune response of those specific T cells against head and neck cancer cell lines was measured in ELISPOT assays. The influence of PD-1 and other immune checkpoints on the peptide-specific immune response was investigated with T cells from healthy donors in conjunction with HNSCC tumor cells. Especially the anti-PD-1 antibody is able to increase antigen-specific immune responses. The combination of anti-PD-1 and other checkpoint inhibitors, like LAG-3 or TIM-3, lead to little or no synergistic effects. Antigen-specific vaccination in combination with PD-1 checkpoint inhibition may therefore be a potential future therapeutic option in head and neck cancer to generate an enhanced anti-tumor immune response. Based on the study findings, an increase antigen-specific immune response by vaccinating the patient with a tumor-associated peptide in combination with anti-PD-1 antibody would be advantageous in HNSCC. Efforts into finding and developing new combination therapies should be further advanced.