Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer
Immune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533740/full |
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| author | Qinyuan Gong Qinyuan Gong Rongzhen Xu Rongzhen Xu |
| author_facet | Qinyuan Gong Qinyuan Gong Rongzhen Xu Rongzhen Xu |
| author_sort | Qinyuan Gong |
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| description | Immune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay to detect serum K102-Env. We then investigated whether K102-Env and K108-Env proteins are present in circulating blood of cancer patients. We found K108-Env proteins were present in serum of both patients with cancer and healthy individuals. In contrast, K102-Env markedly increased in patients with PDAC, hepatocellular carcinoma (HCC), and non-small cell lung cancer (NSCLC) compared with healthy controls. The positive rates of K102-Env were 34.00%, 39%, and 28.0% in PDAC, HCC, and NSCLC, respectively, whereas only 5.0% of healthy individuals had marginally increased K102-Env. In the sera of PDAC patients, K102-Env was 36.63-fold higher than that of healthy controls. K102-Env significantly upregulated PD-1/PD-L1 and c-Myc expression levels of T cells. Importantly, serum K102-Env levels correlated well with advanced cancers and tumor biomarkers CA19-9 and AFP. These findings indicate that circulating K102-Env protein is a novel serum biomarker for evaluating immunosuppressive status and disease stage of patients with cancer. |
| format | Article |
| id | doaj-art-54dc0a8a2c344972b41654ffda8ab05b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-54dc0a8a2c344972b41654ffda8ab05b2025-01-30T09:22:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15337401533740Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancerQinyuan Gong0Qinyuan Gong1Rongzhen Xu2Rongzhen Xu3Department of Hematology and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Hematology, Zhejiang University, Hangzhou, ChinaDepartment of Hematology and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Hematology, Zhejiang University, Hangzhou, ChinaImmune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay to detect serum K102-Env. We then investigated whether K102-Env and K108-Env proteins are present in circulating blood of cancer patients. We found K108-Env proteins were present in serum of both patients with cancer and healthy individuals. In contrast, K102-Env markedly increased in patients with PDAC, hepatocellular carcinoma (HCC), and non-small cell lung cancer (NSCLC) compared with healthy controls. The positive rates of K102-Env were 34.00%, 39%, and 28.0% in PDAC, HCC, and NSCLC, respectively, whereas only 5.0% of healthy individuals had marginally increased K102-Env. In the sera of PDAC patients, K102-Env was 36.63-fold higher than that of healthy controls. K102-Env significantly upregulated PD-1/PD-L1 and c-Myc expression levels of T cells. Importantly, serum K102-Env levels correlated well with advanced cancers and tumor biomarkers CA19-9 and AFP. These findings indicate that circulating K102-Env protein is a novel serum biomarker for evaluating immunosuppressive status and disease stage of patients with cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533740/fullcancer immunosuppressionendogenous retrovirusesHML-2 subtypeHERV-K102serum biomarker |
| spellingShingle | Qinyuan Gong Qinyuan Gong Rongzhen Xu Rongzhen Xu Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer Frontiers in Immunology cancer immunosuppression endogenous retroviruses HML-2 subtype HERV-K102 serum biomarker |
| title | Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| title_full | Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| title_fullStr | Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| title_full_unstemmed | Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| title_short | Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| title_sort | subtype specific human endogenous retrovirus k102 envelope protein is a novel serum immunosuppressive biomarker of cancer |
| topic | cancer immunosuppression endogenous retroviruses HML-2 subtype HERV-K102 serum biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1533740/full |
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