Biology subjects

Schaeuble, K.

Publications and source records attributed to Schaeuble, K..

2 recordsLinked to original sources

bioRxiv2025

Integrated single cell analysis identifies CD39+ tumor-associated NK cells with cytotoxic potential in lung cancer

Natural killer (NK) cell-targeting immunotherapies are emerging, yet the differentiation and functional states of tumor-infiltrating NK cells remain poorly understood. Using matched single-nucleus RNA and ATAC sequencing of non-small cell lung cancer (NSCLC) specimens, we resolved the transcriptional and epigenetic landscape of intratumoral NK cells. We identified two tumor-associated NK (taNK) cell subsets marked by ITGAE (CD103) and ITGA1 (CD49a) that display features of tissue residency and dysfunction while preserving cytotoxic function. Trajectory and regulon analyses revealed an inflammation-driven transition from early GZMK NKs toward an ENTPD1+ (CD39) effector state characterized by interferon-stimulated gene (ISG) programs. Functional profiling established CD39 taNK as the dominant cytotoxic NK cell population with superior killing capacity that is further potentiated by NKG2A blockade. This study offers mechanistic insights into NK cell differentiation in NSCLC and establishes CD39 taNK cells as a targetable effector population for immunotherapy. One sentence summaryMultiomic analysis identifies CD39+ tumor-associated NK cells as a cytotoxic effector state in NSCLC responsive to NKG2A blockade.

immunology↗

bioRxiv2018

Attenuation of chronic antiviral T cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts

Fibroblastic reticular cells (FRC) of lymphoid T zones actively promote T cell trafficking, homeostasis and expansion, but can also attenuate excessive T cell responses via inducible nitric oxide and constitutive prostanoid release. It has remained unclear under which conditions these FRC-derived mediators can dampen T cell responses and whether this occurs in vivo. Here we confirm that murine lymph node FRC produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T cell responses, in contrast to nitric oxide which only comes into play during strong T cell responses. In chronic infections in vivo, PGE2-receptor signaling in virus-specific CD8 T cells was shown by others to suppress T cell survival and function. Using CCL19cre x COX2flox/flox mice we now identify CCL19cre+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRC within lymphoid tissues are an interesting therapeutic target to improve T cell mediated pathogen control during chronic infection.

immunology↗