Biology subjects

Truntzer, C.

Publications and source records attributed to Truntzer, C..

3 recordsLinked to original sources

bioRxiv2026

CASM potentiates STING-driven NFκB signaling in immune cells

Stimulator of Interferon Gene (STING), a key player of antimicrobial immune responses, has emerged as a promising target to mitigate inflammation and cancer. Following STING activation, proinflammatory molecules and type I Interferons (IFN) are released thus favoring the establishment of effective immune responses and adaptive immunity. Autophagy has been proposed to negatively regulate STING signaling. While STING activation drives microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) lipidation, the underlying mechanisms and functional consequences remain however incompletely defined. Especially, the consequences of STING-associated Conjugation of autophagy related (ATG) 8 to Single Membranes (CASM) in the control of immune responses remain elusive. Using innate and adaptive cells specifically inactivated for autophagy or CASM, we found that STING agonists primarily trigger CASM over autophagy. While STING-associated autophagy exerts negative feedback on the STING pathway and downstream type I IFN and pro-inflammatory responses, with different underlying molecular mechanisms between immune cells, STING-driven CASM potentiates NF{kappa}B-associated TNF production. These results overall uncover a new function of CASM and underscore the relevance of both CASM and autophagy in shaping STING signaling

cell biology↗

bioRxiv2024

Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of YAP1 and TEAD-family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications. Therefore, identifying patients with a dysregulated Hippo pathway is key to enhancing treatment impact. Although recent studies have derived RNAseq-based signatures, there remains a need for a reproducible and cost-effective method to measure the pathway activation. In recent years, deep learning applied to histology slides have emerged as an effective way to predict molecular information from a data modality available in clinical routine. Here, we trained models to predict YAP1/TEAD activity from H&E-stained histology slides in multiple cancers. The robustness of our approach was assessed in seven independent validation cohorts. Finally, we showed that histological markers of disease aggressiveness were associated with dysfunctional Hippo signaling.

bioinformatics↗

bioRxiv2021

Effects of tumor mutation burden on the antigen presentation pathway

Tumor mutation burden (TMB) is used to select patients to receive immune checkpoint inhibitors (ICIs) but has mixed predictive capabilities. We hypothesized that inactivation of antigen presenting genes (APGs) that result from increased TMBs would result in inherent resistance to ICIs. We observed that somatic mutations in APGs were associated with increasing TMBs across 9,418 tumor samples of 33 different histological subtypes. In adenocarcinomas of the lung, ITGAX and CD1B were some of the most commonly mutated APGs. In 62 patients with non-small cell lung cancers treated with a PD-1 inhibitor in second or later lines of therapy, there was an association of increased TMB with mutations in APGs; however, mutations in one or more APGs were associated with improved progression-free survival. Contrary to our hypothesis, mutations in APGs were associated with improved progression-free survival with nivolumab, possibly due to the involvement of single alleles rather than complete loss.

immunology↗