Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome.
Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.
Maeda
A
A
Department of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Ohguro
H
H
Nabeta
Y
Y
Hirohashi
Y
Y
Sahara
H
H
Maeda
T
T
Wada
Y
Y
Sato
T
T
Yun
C
C
Nishimura
Y
Y
Torigoe
T
T
Kuroki
Y
Y
Sato
N
N
D000951:Antigens, Neoplasm / Q000276:immunology*; D002135:Calcium-Binding Proteins / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005136:Eye Proteins; D015234:HLA-A Antigens / Q000032:analysis; D059871:HLA-A24 Antigen; D051597:Hippocalcin; D006801:Humans; D007167:Immunotherapy; D008074:Lipoproteins; D009369:Neoplasms / Q000628:therapy; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D011379:Prognosis; D051603:Recoverin; D012164:Retinal Diseases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D002135:Calcium-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005136:Eye Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496731:RCVRN protein, human; D051603:Recoverin; D051597:Hippocalcin