Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer
Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic grou...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460276 |
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| author | Esen Yonca Bassoy Remya Raja Thomas E. Rubino Fabian Coscia Krista Goergen Paul Magtibay Kristina Butler Alessandra Schmitt Ann L. Oberg Marion Curtis |
| author_facet | Esen Yonca Bassoy Remya Raja Thomas E. Rubino Fabian Coscia Krista Goergen Paul Magtibay Kristina Butler Alessandra Schmitt Ann L. Oberg Marion Curtis |
| author_sort | Esen Yonca Bassoy |
| collection | DOAJ |
| description | Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC. |
| format | Article |
| id | doaj-art-04868314281644e5bfb0044346968d23 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-04868314281644e5bfb0044346968d232025-02-01T07:07:03ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2460276Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancerEsen Yonca Bassoy0Remya Raja1Thomas E. Rubino2Fabian Coscia3Krista Goergen4Paul Magtibay5Kristina Butler6Alessandra Schmitt7Ann L. Oberg8Marion Curtis9Department of Immunology, Mayo Clinic, Phoenix, AZ, USADepartment of Immunology, Mayo Clinic, Phoenix, AZ, USADepartment of Immunology, Mayo Clinic, Phoenix, AZ, USAMax-Delbruck-Center for Molecular Medicine in the Helmholtz Association (MDC), Spatial Proteomics Group, Berlin, GermanyDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USADepartment of Obstetrics and Gynecology, Mayo Clinic, Phoenix, AZ, USADepartment of Obstetrics and Gynecology, Mayo Clinic, Phoenix, AZ, USADivision of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USADepartment of Immunology, Mayo Clinic, Phoenix, AZ, USAMost high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460276Cancer immunologyimmunotherapyovarian cancertumor antigen |
| spellingShingle | Esen Yonca Bassoy Remya Raja Thomas E. Rubino Fabian Coscia Krista Goergen Paul Magtibay Kristina Butler Alessandra Schmitt Ann L. Oberg Marion Curtis Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer OncoImmunology Cancer immunology immunotherapy ovarian cancer tumor antigen |
| title | Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer |
| title_full | Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer |
| title_fullStr | Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer |
| title_full_unstemmed | Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer |
| title_short | Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer |
| title_sort | identification of ttll8 potee and pkmyt1 as immunogenic cancer associated antigens and potential immunotherapy targets in ovarian cancer |
| topic | Cancer immunology immunotherapy ovarian cancer tumor antigen |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2460276 |
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