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Hamel, S.

Publications and source records attributed to Hamel, S..

2 recordsLinked to original sources

Climate, caribou and human needs linked by analysis of Indigenous and scientific knowledge

Migratory tundra caribou are ecologically and culturally critical in the circumpolar North. However, they are declining almost everywhere in North America, likely due to natural variation exacerbated by climate change and human activities. Yet, the interconnectedness between climate, caribou, and human well-being has received little attention. To address this gap, we bridged Indigenous and scientific knowledge in a single model, using as example the Porcupine caribou herd social-ecological system. Our analysis, involving 688 (fall season) and 616 (spring season) interviews conducted over nine years with 405 (fall season) and 390 (spring season) Indigenous hunters from nine communities, demonstrates that environmental conditions, large-scale temporal changes associated with caribou demography, and cultural practices affect hunters capacity to meet their needs in caribou. Our quantitative approach bolsters our understanding of the complex relationships between ecosystems and human welfare in environments exposed to rapid climate change, and shows the benefits of long-term participatory research methods implemented by Indigenous and scientific partners.

systems biology↗

Intratumoral mregDC and CXCL13 T helper niches enable local differentiation of CD8 T cells following PD-1 blockade

Here, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+ CH25H+ IL-21+ PD-1+ CD4 T helper cells (CXCL13+ Th) and Granzyme K+ PD-1+ effector-like CD8 T cells, whereas terminally exhausted CD39hi TOXhi PD-1hi CD8 T cells dominated in non-responders. Strikingly, most T cell receptor (TCR) clones that expanded post-treatment were found in pre-treatment biopsies. Notably, PD-1+ TCF-1+ progenitor-like CD8 T cells were present in tumors of responders and non-responders and shared clones mainly with effector-like cells in responders or terminally differentiated cells in non-responders, suggesting that local CD8 T cell differentiation occurs upon ICB. We found that these progenitor CD8 T cells interact with CXCL13+ Th cells within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". Receptor-ligand analysis revealed unique interactions within these triads that may promote the differentiation of progenitor CD8 T cells into effector-like cells upon ICB. These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ Th cells control the differentiation of tumor-specific progenitor CD8 T cell clones in patients treated with ICB.

immunology↗