Biology subjects

Toullec, D.

Publications and source records attributed to Toullec, D..

2 recordsLinked to original sources

bioRxiv2026

The solid tumor microenvironment changes the hierarchy of CD155 and CD112 receptors, shaping checkpoint blockade outcome

Reproducing a physiologically relevant tumor microenvironment in vitro is essential for developing effective immunotherapeutic treatments. By integrating the use of combinatorial receptor blockade and organoid models we provide a deep functional understanding of CD155 and CD112 receptors in solid tumors and their impact on cellular immunotherapy and infiltration. CD226 showed plasticity in response to the environment, being able to switch between CD155 and CD112 depending on the ligand availability. In addition, CD226 drove NK cell infiltration into tumor tissues via CD155 and CD112 ligation, with CD226-CD112 interaction specifically promoting migration from the periphery to the core. Downregulation of CD155 and TIGIT induced by the tumor microenvironment and previous drug exposure reduced the long-term efficacy of TIGIT blockade. Taken together, our findings point towards using CD112R blockade in primary tumors to simultaneously enhance NK cell killing activity and promote infiltration into the tumor core via CD226 and CD112 interaction. ONE SENTENCE SUMMARYTumors shape the hierarchy of CD155-CD112 receptors, reducing TIGIT blockade efficacy, while CD226 drives NK infiltration and shows binding plasticity

immunology↗

bioRxiv2019

Chaperone-mediated ordered assembly of the SAGA transcription complex

Transcription initiation involves the coordinated activities of large multimeric complexes that are organized into functional modules. Little is known about the mechanisms and pathways that govern their assembly from individual components. We report here several principles governing the assembly of the highly conserved SAGA and NuA4 co-activator complexes. Using fission yeast, which contain two functionally non-redundant paralogs of the shared Tra1 subunit, we demonstrate that Tra1 contributes to scaffolding the entire NuA4 complex. In contrast, within SAGA, Tra1 specifically promotes the incorporation of the de-ubiquitination module (DUB), defining an ordered assembly pathway. Biochemical and functional analyses elucidated the mechanism by which Tra1 assemble differentially into SAGA or NuA4 and identified a small, conserved region of Spt20 that is both necessary and sufficient to anchor Tra1 within SAGA. Finally, we establish that Hsp90 and its cochaperone TTT are required for Tra1 de novo incorporation into both SAGA and NuA4, indicating that Tra1, a pseudokinase of the PIKK family, shares a dedicated chaperone machinery with its cognate kinases. Overall, our work brings mechanistic insights into the de novo assembly of transcriptional complexes through ordered pathways and reveals the contribution of dedicated chaperones to this process.

biochemistry↗