Spielvogel, C. | Search bioRxiv

bioRxiv2026

Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer

Amygdala metabolic activity (AmygAc) measured by [18F]FDG PET has been associated with chronic psychological stress and adverse clinical outcomes, but its relationship with antitumor immunity and treatment response remains incompletely understood. We investigated AmygAc as a host-derived imaging biomarker in non-small cell lung cancer (NSCLC) and examined its association with survival, response to immune checkpoint inhibition (ICI), and the tumor immune microenvironment. Methods: In this multicenter retrospective study, baseline [18F]FDG PET scans from 256 treatment-naive patients with NSCLC were analyzed to quantify AmygAc. Overall survival was assessed in the full cohort, and treatment response was evaluated in 79 patients who subsequently received neoadjuvant ICI therapy. AmygAc was integrated with clinical and tumor-derived imaging parameters. To investigate its biological correlates, tumor tissue from a selected subcohort was analyzed using multiplex immunofluorescence and spatial transcriptomics.

cancer biology↗

bioRxiv2025

Thyroid Hormone Receptor Beta Signaling is a Targetable Driver of Prostate Cancer Growth

Thyroid hormone (TH) signaling plays a major role in the development, energy homeostasis, and metabolism of most tissues. Recent observations have identified THs as drivers of prostate cancer (PCa) tumor development and progression. We reported that the T3-scavenger protein {micro}-crystallin (CRYM) regulates the development and progression of PCa and that this involved crosstalk with the androgen receptor (AR) signaling. However, the mechanisms remain incompletely understood. Here, we explored the role of thyroid hormone receptor {beta} (TR{beta}), which is the main effector of TH signaling, in the context of PCa. The use of the TR{beta}-selective antagonist NH-3 inhibited PCa cell proliferation in vitro and reduced tumor size in PCa xenograft models. Notably, NH-3 was highly effective in the engrafted 22Rv1 cell line, a model for castration-resistant PCa (CRPC). Mechanistic studies revealed that NH-3 downregulates AR and the AR target genes Nkx3.1 and KLK3 (PSA). NH-3 was a more effective anticancer agent than enzalutamide and showed synergistic properties in combined use. Evidence from human datasets corroborates our findings whereby elevated TR{beta} expression and mutations in TH signaling pathways are associated with the onset of PCa. Collectively, these results establish TR{beta} as a mediator of tumorigenesis in PCa and identify NH-3 as a promising therapeutic agent for targeting AR signaling, particularly in CRPC.

cancer biology↗