Expressions of cancer-testis antigens in human hepatocellular carcinomas

Chen, Chien‐Hung; Chen, Guann-Jou; Lee, Hsuan-Shu; Huang, Guan-Tarn; Yang, Pei‐Ling; Tsai, Li-Jen; Chen, Ding‐Shinn; Sheu, Jin‐Chuan

doi:10.1016/s0304-3835(01)00379-2

Cited by 54 publications

(41 citation statements)

References 28 publications

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“…In 325 specimens of human neoplasms from various histological origins, expression of SSX-4 was found in 15% of all tumors, including 10 of 48 (20.8%) malignant melanomas tested (7). More recently expression of SSX-4 has been reported by us (9) in 23% of sarcomas and by others in several different tumor types, such as 73% of hepatocellular carcinomas (8), 35% of primary lung cancers (10), 67% of neuroblastomas (11), and 20% of gastric carcinomas (12).…”

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confidence: 89%

“…Recently, SSX genes and pseudogenes have been further characterized, resulting in the definition of nine (SSX-1 to -9) genes (6). Expression of the majority of the SSX genes, including SSX-1 to -5 and SSX-7, is restricted to gametogenic cells, not found in most adult normal tissues, but is detected in tumors of different histological types (7)(8)(9). Therefore, Ags of the SSX family are targets of interest for immunotherapy of cancer.…”

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confidence: 99%

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CD4+ T Cell Responses to SSX-4 in Melanoma Patients

Ayyoub¹,

Merlo²,

Hesdorffer

et al. 2005

The Journal of Immunology

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T he synovial sarcoma X breakpoint (SSX)3 genes are located on the X chromosome and encode a family of highly homologous nuclear proteins. Two family members, SSX-1 and SSX-2 were initially identified as fusion partners of the SYT gene in t(X;18)-positive synovial sarcomas (1, 2). Later, serological analysis of tumor cDNA expression libraries (SEREX), revealed recognition of the SSX-2 encoded Ag by Abs from cancer patients (3). Three additional homologous genes, SSX-3, -4, and -5, were identified (4, 5) either through screening of a testicular cDNA library with allogeneic patient serum (SSX-3 (5)) or by analysis of homologous sequences amplified by SSX-specific primers (SSX-3 (4), SSX-4, and -5 (5)). Recently, SSX genes and pseudogenes have been further characterized, resulting in the definition of nine (SSX-1 to -9) genes (6). Expression of the majority of the SSX genes, including SSX-1 to -5 and SSX-7, is restricted to gametogenic cells, not found in most adult normal tissues, but is detected in tumors of different histological types (7-9). Therefore, Ags of the SSX family are targets of interest for immunotherapy of cancer.Among SSX genes, SSX-1, -2, -4, and -5 are the most commonly expressed. Surveys of SSX gene expression in different human tumor types have shown expression of several family members in a significant proportion of tumors, although at variable levels depending on the particular histological type. In 325 specimens of human neoplasms from various histological origins, expression of SSX-4 was found in 15% of all tumors, including 10 of 48 (20.8%) malignant melanomas tested (7). More recently expression of SSX-4 has been reported by us (9) in 23% of sarcomas and by others in several different tumor types, such as 73% of hepatocellular carcinomas (8), 35% of primary lung cancers (10), 67% of neuroblastomas (11), and 20% of gastric carcinomas (12).We have previously reported that one Ag of the family, SSX-2, is naturally immunogenic in cancer patients bearing Ag-expressing tumors, and identified both CD8 ϩ and CD4 ϩ SSX-2-derived T cell epitopes (13-15). However, no information was thus far available on T cell responses to other SSX Ags. Here, we report the analysis of CD4 ϩ T cell responses against SSX-4, in melanoma patients. Upon in vitro stimulation with a pool of long peptides spanning the protein sequence, we could detect and isolate SSX-4-specific CD4 ϩ T cells from four melanoma patients bearing Agexpressing tumors. We isolated SSX-4-specific clonal CD4 ϩ T cell populations recognizing several distinct antigenic sequences restricted by different HLA class II alleles including some among the HLA-DR alleles more frequently expressed in several major ethnic groups. Interestingly, the majority of the identified sequences were located within the Krüppel-associated box (KRAB) repression domain in the N-terminal region of the protein.

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confidence: 89%

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confidence: 99%

CD4+ T Cell Responses to SSX-4 in Melanoma Patients

Ayyoub¹,

Merlo²,

Hesdorffer

et al. 2005

The Journal of Immunology

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“…The malignant transformation of these antigens is frequently associated with the activation or depression of genes, resulting in the expression of the antigens. More than 50 types of CTA have been identified thus far, including MAGE, GAGE, PAGE, NY-ESO-1, SSX, SPANX and XAGE (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular carcinoma patients highly and specifically expressing XAGE-1 exhibit prolonged survival

et al. 2010

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Abstract. XAGE-1 is classified into the group of a new family of cancer-testis antigens (CTA) and has the four transcript variants of XAGE-1a, XAGE-1b, XAGE-1c and XAGE-1d. Immunohistochemistry was used to investigate the expression of XAGE-1 transcript variants in Chinese patients with hepatocellular carcinoma (HCC). Reverse transcriptionpolymerase chain reaction (RT-PCR) and real-time RT-PCR were used to analyze XAGE-1 gene expression, and XAGE-1 protein expression was examined by immunohistochemistry. Furthermore, the clinical correlation of XAGE-1 expression was analyzed. The expression of the XAGE-1 mRNA was investigated in the tissues of 96 HCC patients and all XAGE-1 isoforms were detected in these tissues. Three types of XAGE-1 transcript variants (XAGE-1b, XAGE-1c and XAGE-1d) showed high specific and frequent expression in HCC tissues, with the positive expression rate of XAGE-1b, XAGE-1c and XAGE-1d being 41.7% (40/96), 15.6% (15/96) and 26.0% (25/96), respectively. XAGE-1b was the dominant type, but none of the three were detected in adjacent non-HCC tissues. Only 2 cases of XAGE-1a mRNA expression were observed. Moreover, XAGE-1 protein was detected in 39 of 96 HCC patients, but none in the adjacent non-cancerous tissue and normal liver tissue. No relationship was found between the expression of XAGE-1 and clinical parameters, such as age, gender, tumor size, TNM staging, serum AFP level and infection with hepatitis virus. Patients with XAGE-1b-positive transcript variant exhibited shorter 2-year survival times. The high frequency and specificity of XAGE-1, particularly XAGE-1b, in HCC indicates that their products may predict the prognosis of HCC patients and be novel targets for antigen-specific immunotherapy to HCC.

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“…Our own data have revealed that mRNA for at least 20 CT antigens can be detected in HCC tissues. Expressed genes include MAGE-A1 (11), MAGE-A3 (12), CTP11, SSX1, HCA587 (MAGE-C2), and FATE-BJ-HCC-2 (13), each of which is expressed in 60% to 80% of HCC specimens, together with NY-ESO-1, MAGE-A4, MAGE-10, SSX-4, SSX2, and SCP-1 mRNAs, each of which is expressed in 30% to 49% of HCC specimens. Immunotherapy directed against these antigens thus represents a potential alter-native for the treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%