Background 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.
Methods 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).
Results 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 (figure 4).
Conclusions Combined radio-immunotherapy can enhance specific T cell responses to the NY-ESO-1 antigen that correlates with beneficial clinical outcome of the patient.
Acknowledgements We acknowledge Dr. Mohamed Elkhalifa and Ms. Zahra Abdi Ashur, from the histocompatibility and immunogenetics laboratory at Hamad Medical Corporation (HMC), for performing HLA-typing on patient‘s blood sample. We acknowledge Dr. Prem Chandra for his help in the statistical analysis. We are grateful to the patient for his participation to the study and to the MRC at HMC for funding this project. We acknowledge Qatar National Library for supporting the publication
Trial Registration NOT applicable
Ethics Approval The study was approved by the Institutional Review board committee of Hamad Medical Corporation, Doha, Qatar.
Consent The patient signed an informed consent form to carry out the study and to publish the data.
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