463 Metastatic gastric cancer patient benefiting from combined radio-immunotherapy treatment displayed sustained anti-NY-ESO-1 specific T cells and expressed important immuno-modulatory markers

Abstract

Combined radio-immunotherapy is currently being investigated to treat cancer patients. Anti-PD-1 immunotherapy offers the prospect of long-term disease control in solid tumors. Radiotherapy has the ability to promote immunogenic cell death leading to the release of tumor antigens, increasing infiltration and activation of T cells. NY-ESO-1 is a cancer-testis antigen expressed in 20% of advanced gastric cancers and known to induce humoral and cellular immune responses in cancer patients. We report on the dynamic immune response to the NY-ESO-1 antigen and important immune-related biomarkers in a metastatic gastric cancer patient treated with radiotherapy combined with anti-PD-1 pembrolizumab antibody. Our patient was an 81-year-old male diagnosed with locally advanced unresectable MMR-deficient gastric cancer having progressed to a metastatic state under a second line of systemic treatment consisting of an anti-PD-1 pembrolizumab antibody. The patient was subsequently treated by local radiotherapy administered concomitantly with anti-PD-1, with a complete response on follow-up radiologic assessment. Disease control was sustained with no further therapy for a period of 12 months before relapse (figure 1). We have identified an NY-ESO-1-specific IFN-? secretion from the patients T cells that was significantly increased at response (****p?0.0001) (figure 2). A novel promiscuous immunogenic NY-ESO-1 peptide P39 (P153-167) restricted to the 4 patient‘s HLA-DQ and HLA-DP alleles was identified. Interestingly, this peptide contained the known NY-ESO-1-derived HLA-A2-02:01(P157-165) immunogenic epitope. We have also identified a CD107+ cytotoxic T cells subset within a specific CD8+/HLA-A2-NY-ESO-1 T cell population that was low at disease-progression, markedly increased at disease-resolution and significantly decreased again at disease-re-progression (figure 3). Finally, we identified 2 groups of cytokines/chemokines. Group 1 contains 5 cytokines (IFN-?, TNF-a, IL-2, IL-5 and IL-6) that were present at disease progression, significantly downregulated at disease resolution and dramatically upregulated again at disease re-progression. Group 2 contains 4 biomarkers (Perforin, sFAS, MIP-3a and CXCL-11/ITAC) that were present at disease progression, significantly upregulated at disease resolution and dramatically downregulated again at disease re-progression