Immune checkpoint inhibitors offer the prospect of long term disease control in solid tumor types. NY-ESO-1 is a cancer-testis antigen expressed by 20% of advanced gastric cancers, known to induce humoral and cellular immune responses. Combination of anti-PD-1 with radiotherapy is currently investigated. Radiotherapy has the ability to promote immunogenic cell death leading to the release of tumor antigens, increasing infiltration and activation of T cells. In this study, we investigated the immune response to the NY-ESO-1 antigen in metastatic gastric cancer treated with anti-PD-1 (pembrolizumab).
T cells response to the NY-ESO-1 antigen was investigated by ELISPOT against NY-ESO-1 PepMix, against the 43 single peptides overlapping the NY-ESO-1 whole protein and the NY-ESO-1 HLA-A2 restricted peptide. The IEDB1 prediction database was used to predict the patient’s HLA DR, DQ and DP binding to NY-ESO-1. We subsequently characterized the phenotypic and functional activity of the patient T cells using flow cytometry analysis.
We have identified a novel promiscuous immunogenic NY-ESO-1 peptide restricted to the 4 HLA-DQ and HLA-DP alleles and containing the known NY-ESO-1 HLA-A2-02:01 (P157-165) immunogenic epitope. CD8+ T cells were increased during combined therapy and at disease resolution in which its PD-1+CD8+ subset was increased during combined therapy and resolution then decreased at disease progression. The CD107+ cytotoxic subset of the CD8+/HLA-A2-NY-ESO-1-dextramer+ T cells was markedly increased during combined therapy and at resolution then dramatically decreased at re-progression.
We have identified a novel promiscuous anti-NY-ESO-1 immunogenic CD4+ peptide containing the P157-165 HLA-A*02:01/CD8+ epitope that was highly presented at disease resolution and decreased at progression after combined radiotherapy/anti-PD-1 immunotherapy. Our study showed that radiation therapy combined with immune checkpoint blockade would enhance the immune response that correlates with the patient clinical outcome.
Hamad Medical Corporation.
Hamad Medical Corporation.
All authors have declared no conflicts of interest.