Happy to collaborate on this study profiling the existence and development of cross-tissue #ILC1 in humans.
https://doi.org/10.1016/j.celrep.2022.111937
Key Takeaways:
-Human ILC1 are rare in healthy liver, but accumulate in cirrhotic livers.
-Unknown #LSEC-derived signals + #TGFβ1 + #il7 drive differentiation of ILC progenitors to ILC1.
-Human #NK cells do not differentiate to ILC1 under multiple conditions ex vivo.
-Human ILC1 make #il2 but functional relevance of this still unknown.
We replicate the lead #GWAS association for #immunotherapy toxicities at #IL7. We find B cells express IL7 which is induced markedly in #melanoma, w. a bigger effect in risk allele carriers. This signature is associated with B cell maturation. Post treatment, risk allele carriers have increased CD8 T cell cytotoxicity & clonality. Notably, the risk allele is associated with lower progression rates in #TCGA. The work places B cells & IL7 in responses to immunotherapy.
Genetic analyses in a cohort of patients with melanoma receiving immunotherapy reveal that variants in IL7 are associated with immune-related adverse events and highlight the role of B cells in mediating toxicity.
O'Sullivan Lab
FairfaxLab