Project description:Immune escape is a prerequisite of tumor growth. We previously described a decline in intratumor activated GZMB+CD8+ T cells and T cell receptor (TCR) clonotype diversity in invasive compared to in situ (DCIS) breast carcinomas implying a role for decreasing TCR diversity in tumor progression. Here, we evaluated peripheral blood TCR clonotype diversity in breast cancer patients diagnosed with DCIS or de novo stage IV disease at different ages. We found that peripheral TCR diversity is associated with clinicopathologic, and peripheral immune status and it correlates with the frequency of CD8+ T cells in DCIS of young patients. These results provide new insights to the role of host immunity and breast cancer development in different aged women.
Project description:Immune escape is a prerequisite of tumor growth. We previously described a decline in intratumor activated GZMB+CD8+ T cells and T cell receptor (TCR) clonotype diversity in invasive compared to in situ (DCIS) breast carcinomas implying a role for decreasing TCR diversity in tumor progression. Here, we evaluated peripheral blood TCR clonotype diversity in breast cancer patients diagnosed with DCIS or de novo stage IV disease at different ages. We found that peripheral TCR diversity is associated with clinicopathologic, and peripheral immune status and it correlates with the frequency of CD8+ T cells in DCIS of young patients. These results provide new insights to the role of host immunity and breast cancer development in different aged women.
Project description:Immune escape is a prerequisite of tumor growth. We previously described a decline in intratumor activated GZMB+CD8+ T cells and T cell receptor (TCR) clonotype diversity in invasive compared to in situ (DCIS) breast carcinomas implying a role for decreasing TCR diversity in tumor progression. Here, we evaluated peripheral blood TCR clonotype diversity in breast cancer patients diagnosed with DCIS or de novo stage IV disease at different ages. We found that peripheral TCR diversity is associated with clinicopathologic, and peripheral immune status and it correlates with the frequency of CD8+ T cells in DCIS of young patients. These results provide new insights to the role of host immunity and breast cancer development in different aged women.
Project description:The brushtail possum, Trichosurus vulpecula, is threatened in parts of its native range in Australia, but has also become a devastating mammalian pest following introduction into New Zealand from the mid 1800s. We have completed the first chromosome-level assembly of the possum genome and, using nuclear and mitochondrial analyses, traced southern New Zealand possums to distinct Tasmanian and mainland Australian subspecies, which have subsequently hybridised. This admixture is reflected in high levels of genetic diversity within New Zealand populations despite a founding bottleneck. Functional genomics revealed unique adaptations to altricial birth and extending weaning, including novel chemo-sensory genes, and at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We found that reprogramming of possum germline imprints and the wider epigenome was similar to eutherian mammals, except onset occurs after birth. Together, our data and analysis is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits such as germline methylation erasure and genomic imprinting.
Project description:The brushtail possum, Trichosurus vulpecula, is threatened in parts of its native range in Australia, but has also become a devastating mammalian pest following introduction into New Zealand from the mid 1800s. We have completed the first chromosome-level assembly of the possum genome and, using nuclear and mitochondrial analyses, traced southern New Zealand possums to distinct Tasmanian and mainland Australian subspecies, which have subsequently hybridised. This admixture is reflected in high levels of genetic diversity within New Zealand populations despite a founding bottleneck. Functional genomics revealed unique adaptations to altricial birth and extending weaning, including novel chemo-sensory genes, and at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We found that reprogramming of possum germline imprints and the wider epigenome was similar to eutherian mammals, except onset occurs after birth. Together, our data and analysis is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits such as germline methylation erasure and genomic imprinting.