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


METHODS
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-gamma ELISPOT assay.


RESULTS
COA-1-specific and tumor-reactive T lymphocytes were isolated from all (n = 7) HLA-DRbeta1*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-1 can occur in colorectal cancer patients with metastatic disease, suggesting that this antigen is suitable for immunotherapeutic protocols of these patients.
Maccalli
Cristina
C
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanitá, Italy. maccalli.cristina@hsr.it
Di Cristanziano
Veronica
V
Fodale
Valentina
V
Corsi
Domenico
D
D'Agostino
Giuseppina
G
Petrangeli
Valentina
V
Laurenti
Luca
L
Guida
Sofia
S
Mazzocchi
Arabella
A
Arienti
Flavio
F
Perrone
Maria P
MP
Castelli
Chiara
C
Rivoltini
Licia
L
Zagonel
Vittorina
V
Tartaglia
Marco
M
Parmiani
Giorgio
G
Belardelli
Filippo
F
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C479798:colorectal tumor-associated antigen, human; D007371:Interferon-gamma