Bassoy Esen Yonca, Raja Remya, Rubino Thomas E, Coscia Fabian, Goergen Krista, Magtibay Paul, Butler Kristina, Schmitt Alessandra, Oberg Ann L, Curtis Marion
Department of Immunology, Mayo Clinic, Phoenix, AZ, USA.
Max-Delbruck-Center for Molecular Medicine in the Helmholtz Association (MDC), Spatial Proteomics Group, Berlin, Germany.
Oncoimmunology. 2025 Dec;14(1):2460276. doi: 10.1080/2162402X.2025.2460276. Epub 2025 Jan 31.
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.
大多数高级别浆液性卵巢癌（OC）对当前的免疫疗法无反应。为了在OC中鉴定潜在的新的可作用肿瘤抗原，我们对表达HLA-A02:01单倍型的人OC细胞系进行了免疫肽组学分析，该单倍型在许多种族和民族中普遍表达。从这个数据集中，我们鉴定出TTLL8、POTEE和PKMYT1肽作为候选肿瘤抗原，它们在正常组织中低表达，在OC中表达上调。使用组织微阵列，我们评估了TTLL8和POTEE的蛋白表达及其与一大群OC患者的患者预后的关联。发现TTLL8在56.7%的OC中表达，并且与较差的总体预后相关。POTEE在97.2%的OC患者中表达，与生存无显著关联。在患者肿瘤浸润淋巴细胞（TILs）中，细胞因子产生和四聚体阳性群体的增加确定了抗原特异性CD8 T细胞反应，这依赖于HLA I类分子的抗原呈递。抗原特异性T细胞触发了对抗原脉冲OC细胞的癌细胞杀伤。这些发现表明，TTLL8、POTEE和PKMYT1是OC中抗原靶向免疫疗法开发的潜在靶点。
