Induction of both CD8+ and CD4+ T-cell-mediated responses in colorectal cancer patients by colon antigen-1

Cristina Maccalli, Veronica Di Cristanziano, Valentina Fodale, Domenico Corsi, Giuseppina D'Agostino, Valentina Petrangeli, Luca Laurenti, Sofia Guida, Arabella Mazzocchi, Flavio Arienti, Maria P. Perrone, Chiara Castelli, Licia Rivoltini, Vittorina Zagonel, Marco Tartaglia, Giorgio Parmiani, Filippo Belardelli

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Abstract

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

Original languageEnglish
Pages (from-to)7292-7303
Number of pages12
JournalClinical Cancer Research
Volume14
Issue number22
DOIs
Publication statusPublished - 15 Nov 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Maccalli, C., Di Cristanziano, V., Fodale, V., Corsi, D., D'Agostino, G., Petrangeli, V., Laurenti, L., Guida, S., Mazzocchi, A., Arienti, F., Perrone, M. P., Castelli, C., Rivoltini, L., Zagonel, V., Tartaglia, M., Parmiani, G., & Belardelli, F. (2008). Induction of both CD8+ and CD4+ T-cell-mediated responses in colorectal cancer patients by colon antigen-1. Clinical Cancer Research, 14(22), 7292-7303. https://doi.org/10.1158/1078-0432.CCR-08-0832