Data from Induction of Both CD8<sup>+</sup> and CD4<sup>+</sup> T-Cell–Mediated Responses in Colorectal Cancer Patients by Colon Antigen-1

Abstract

<div>Abstract<p><b>Purpose:</b> Colon antigen-1 (COA-1) was recently identified as a novel antigen of colorectal cancer encoded by the <i>UBXD5</i> gene. Here, we evaluated whether a specific T-cell-mediated response directed against this molecule can occur in colorectal cancer patients.</p><p><b>Experimental Design:</b> Antigen- and tumor-specific immunologic responses of peripheral blood mononuclear cells (PBMC) stimulated <i>in vitro</i> with the MHC class II-associated immunogenic epitope of COA-1 (FSTFPPTLYQDDTLTLQAAG) were analyzed by IFN-γ ELISPOT assay.</p><p><b>Results:</b> COA-1-specific and tumor-reactive T lymphocytes were isolated from all (<i>n</i> = 7) HLA-DRβ1*0402<sup>+</sup> or *1301<sup>+</sup> colorectal cancer patients with progressive disease (Dukes' C and D) but not in patients (<i>n</i> = 4) with early-stage tumor (Dukes' A and B) and in healthy donors (<i>n</i> = 5), suggesting that the immune response against this antigen is associated with the progression of colorectal cancer. COA-1- and tumor-specific T lymphocytes displayed a CD3<sup>+</sup>CD4<sup>+</sup>CD69<sup>+</sup>CD45RA<sup>+</sup> phenotype, compatible with the activated effector-type T-cell subset, and most of them exerted cytotoxic activity against HLA-matched and COA-1<sup>+</sup> tumor cells. COA-1-specific T cells could also be isolated by <i>in vitro</i> stimulation of peripheral blood mononuclear cells with autologous dendritic cells loaded with tumor lysate, suggesting that this antigen can generate a dominant immunologic response against colorectal cancer cells. Notably, we could identify also COA-1-derived epitopes binding to HLA-A*0201 molecules that elicited antigen- and tumor-specific CD8<sup>+</sup> T-cell-mediated responses in colorectal cancer patients.</p><p><b>Conclusions:</b> Both CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses against COA-1 can occur in colorectal cancer patients with metastatic disease, suggesting that this antigen is suitable for immunotherapeutic protocols of these patients.</p></div>