Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian... Show moreDespite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3(+) CD8(+)CD103(+)CD69(+) TRM cells and immunohistochemistry of 122 high-grade serous ovarian cancers shows that only progenitor (TCF1(low)) tissue-resident T cells (TRMstem cells), but not recirculating TCF1(+) T cells, predict ovarian cancer outcome. TRMstem cells arise from transitional recirculating T cells, which depends on antigen affinity/persistence, resulting in oligoclonal, trogocytic, effector lymphocytes that eventually become exhausted. Therefore, ovarian cancer is indeed an immunogenic disease, but that depends on similar to 13% of CD8(+) tumor-infiltrating T cells (similar to 3% of CD8(+) clonotypes), which are primed against high-affinity antigens and maintain waves of effector TRM-like cells. Our results define the signature of relevant tumor-reactive T cells in human ovarian cancer, which could be applicable to other tumors with unideal mutational burden. Show less
Neyer, G.; Thévenon, O.; Digoix, M.; Cortina, C.; Festy, P.; Waaldijk, C.; ... ; Hellgren, Z. 2017
This document summarizes the main findings from the research carried out in Workpackage 9, Policies and Diversity over the Life Course, within the FamiliesAndSocieties project. We present key... Show moreThis document summarizes the main findings from the research carried out in Workpackage 9, Policies and Diversity over the Life Course, within the FamiliesAndSocieties project. We present key results from our studies (1) on policies directed to young people at the transition to adulthood and self-sufficient living, (2) on preferences, usage, and consequences of parental-leave and fathers’ leave policies on family dynamics; (3) on the legal family formats for same-sex and/or different-sex couples in European countries, (4) on the emergence of private markets and issues of migration and care, and (5) on European Union family-policy initiatives. In our summary, we focus on policy-relevant findings and in particular on those of broader implications for policies, policy directions, and policy design in Europe at large. In concluding we summarize some of the core policy implications of our studies.See also www.familiesandsocieties.eu and www.lawsandfamilies.eu. Show less
