Tissue transglutaminase as a new immunomodulatory target in ovarian cancer tumor microenvironment

作者：Livia Elena Sima, Siqi Chen, Horacio Cárdenas, Guangyuan Zhao, Yinu Wang, Cristina Ivan, Hao Huang, Bin Zhang, Daniela Matei · 发表于：South East European Journal of Immunology · 年份：2025 · DOI：10.3889/seejim.2025.6127 · 被引用次数：1 · 研究领域：Blood properties and coagulation

Tissue transglutaminase (TG2) is a multifunctional protein with roles in multiple diseases including cancer. It was found overexpressed in many solid tumors in the past two decades. In ovarian cancer, it emerged as a potential therapeutic target due to its involvement in processes like metastasis and chemo- and radiotherapy resistance. Generally, TG2 expression in cancer cells has been extensively studied and linked to increased tumor progression. However, its role in the host was less studied. Our research explored the anti-tumor immune response using a TG2KO syngeneic ovarian cancer mouse model, as compared to wild-type animals. We observed decreased tumor burden and increased survival upon i.p. injection of ID8 mouse ovarian cancer cells in TG2KO mice, as compared to wild-type. In the absence of TG2 in the host, an increased infiltration of CD8+ T cells in ascites was evidenced by FACS, while myeloid cells were less present. The TG2KO CD8+ T cells showed increased activation and increased effector function. Moreover, these cells showed an increased cancer cell killing capacity. At the molecular level, this phenotype was supported by attenuated STAT3 phosphorylation. Cancer cells in ascites collected from TG2KO mice showed a gene signature corresponding to IFN-γ response. Overall, these data show decreased tumor progression and increased effector phenotype in CD8+ T cells when TG2 is absent in the host (Sima LE et al. (2021) Journal for ImmunoTherapy of Cancer 9, e002682). ...