[Research Articles] Characterization of ascites- and tumor-infiltrating {gamma}{delta} T cells reveals distinct repertoires and a beneficial role in ovarian cancer

The role of T cells in antitumor immunity has been under investigation for the past two decades, but little is known about their contribution to clinical outcomes in patients. Here, we set out to define the clonotypic, phenotypic, and functional features of T cells in peripheral blood, ascites, and metastatic tumor tissue from patients with advanced epithelial ovarian cancer. T cell receptor (TCR) sequencing of the chain revealed that tumor-infiltrating T cells have a unique and skewed repertoire with high TCR diversity and low clonality. In contrast, ascites-derived T cells presented a lower TCR diversity and higher clonality, suggesting a TCR-dependent clonal focusing at this site. Further investigation showed that tumor samples had abundant T cells with a tissue-resident, activation-associated phenotype, less usage of V9 and an impaired response to adaptive-associated stimuli, implying an innate-like activation pathway, rather than an adaptive TCR-engaging pathway, at these tumor sites. Furthermore, high T cell cytokine responsiveness upon stimulation was associated with a favorable outcome for patients in terms of both overall survival and reduced residual tumor burden after primary surgery. Last, the functionality of T cells and patient survival were negatively affected by the proportions of CD39-expressing T cells, highlighting the potential of CD39 as a target to improve T cell responses and unleash their antitumor capabilities.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research