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Immune Responses to the Cancer Testis Antigen XAGE-1b in Non Small Cell Lung Cancer Caucasian Patients
Authors:Kanako Saito  Eiichi Nakayama  Danila Valmori
Affiliation:1Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l’Ouest, Nantes-Saint Herblain, France;2Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Japan;3Faculty of Medicine, University of Nantes, Nantes, France;Mie University Graduate School of Medicine, JAPAN
Abstract: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.
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