Immune Responses to the Cancer Testis Antigen XAGE-1b in Non Small Cell Lung Cancer Caucasian Patients

Immunotherapy approaches using checkpoint blockade, alone, or in combination with tumor antigen vaccination, or adoptive cell transfer, are emerging as promising approaches for the treatment of non-small cell lung cancer (NSCLC). In preparation for upcoming combined immunotherapy approaches in NSCLC, here, we have assessed spontaneous immune responses to XAGE-1b, a tumor specific antigen of the Cancer Testis Antigen group that has been previously reported to be spontaneously immunogenic in the Japanese population, in a cohort of Caucasian patients with NSCLC. We found spontaneous serological responses to XAGE-1b in 9% of the patients. Importantly, these responses were limited to, and represented 13% of, patients with adenocarcinoma tumors, the most frequent histological subtype, for which immunotherapy approaches are under development. Using a set of overlapping peptides spanning the entire XAGE-1b protein, and in support of the serological data, we detected significant XAGE-1b specific CD4(+) T cell responses in all XAGE-1b seropositive patients and identified several CD4(+) T cell epitopes. Altogether, our results support the relevance of the XAGE-1b antigen in Caucasians NSCLC patients with adenocarcinoma, and the implementation of future immunotherapies exploiting the high immunogenicity of the antigen in this patient population.