XAGE-1 Expression in Non–Small Cell Lung Cancer and Antibody Response in Patients

Abstract

Purpose: XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens. Four transcript variants XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d have been identified thus far.We recently identified XAGE-1b as a dominant antigen recognized by sera from lung adenocarcinoma patients.We here investigated the mRNA expression of four XAGE-1variants and XAGE-1protein expression in non^small cell lung cancer (NSCLC). Humoral immune response to XAGE-1b was also evaluated in patients. Experimental Design: Forty-nine NSCLC specimens were analyzed for the expression of four XAGE-1 transcript variants by conventional 30-cycle and real-time reverse transcription-PCR and XAGE-1 protein expression by immunohistochemistry. Sera from 74 patients were analyzed for XAGE-1b antibody production by ELISA and Western blot. Results: XAGE-1b and XAGE-1d mRNA were detected in 15 and 6 of 49 lung cancer specimens, respectively. No XAGE-1a or XAGE-1c mRNA expression was observed. XAGE-1b mRNA expression was observed in 14 of 31 (45%) adenocarcinoma and 1 of 18 (6%) lung cancer with other histologic types. Immunohistochemical analysis using a XAGE-1 monoclonal antibody showed that 14 of 15 XAGE-1b mRNA-positive and 3 of 34 XAGE-1b mRNA-negative specimens expressed XAGE-1protein. Seropositivity was observed in 5 of 56 patients with adenocarcinoma, whereas none of 18 patients with other histologic types produced XAGE-1b antibody. Conclusion: XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.

Seromic profiling of ovarian and pancreatic cancer

“…For example, antibodies to NY-ESO-1 are found in ≈50% of stage IV melanoma patients expressing NY-ESO-1 in their tumor, but the overall frequency in melanoma is about 8% when considering earlier stages (with less frequent NY-ESO-1 expression) and nonexpressing tumors (31). Similarly, p53 and XAGE-1 are immunogenic in 10-30% of non-small-cell lung cancers, depending on type and stage, but very rarely so in melanoma (35)(36)(37). Therefore, in the current study, the frequencies of seroreactivity observed against top antigens in pancreatic and ovarian cancer patients have to be placed in the context of cognate antigen expression frequency, tumor type selected, and stage.…”

Identification of CCDC62‐2 as a novel cancer/testis antigen and its immunogenicity

“…30,31 We have shown similar antibody responses in patients with XAGE-1b-expressing lung cancer. 32 However, antibody responses were observed in less than 1% of patients against other CT antigens, e.g., MAGE-1. 26 Our study demonstrated the immunogenicity of CCDC62-2 by examining serum reactivity by ELISA using recombinant protein.…”

HLA‐DRB1*0410‐Restricted Recognition of XAGE‐1b37‐48 Peptide by CD4 T Cells

“…Transfection with mRNA was shown to be able to present the antigen naturally to not only CD8 but also CD4 T cells (16,17,20). XAGE-1b mRNA was shown to be expressed frequently in non-small cell lung cancer (15/49, 31%), liver cancer (11/19, 58%), and prostate cancer (14/54, 24%), and less frequently in breast cancer (1/20, 5%) (12,18). In lung cancer, a high frequency of XAGE-1b mRNA expression was observed in adenocarcinoma (14/31, 45%) (18).…”

“…XAGE-1b mRNA was shown to be expressed frequently in non-small cell lung cancer (15/49, 31%), liver cancer (11/19, 58%), and prostate cancer (14/54, 24%), and less frequently in breast cancer (1/20, 5%) (12,18). In lung cancer, a high frequency of XAGE-1b mRNA expression was observed in adenocarcinoma (14/31, 45%) (18). XAGE-1b protein expression was observed immunohistochemically in most XAGE-1b mRNA-expressing lung cancers (18).…”