Talent and passion carried this dance company’s annual concert — but pushing the envelope would carry it further

The tumor microenvironment (TME) is increasingly understood as a metabolically dynamic ecosystem in which local metabolite availability, composition, and trafficking shape immune cell fitness and therapeutic responsiveness. Against the backdrop of the global obesity epidemic, obesity-associated systemic metabolic dysregulation has been implicated in tumor initiation and progression and may also influence the immune contexture and treatment responsiveness of tumors. This Review examines how obesity-derived systemic metabolites may modulate anti-tumor immunity and influence cancer immunotherapy, with particular emphasis on pathways involved in metabolic reprogramming and TME remodeling. We further discuss intervention strategies spanning (i) upstream metabolite generation, (ii) systemic-to-local trafficking into the TME, and (iii) direct functional antagonism within the TME. However, the available evidence remains heterogeneous across metabolite classes, tumor types, and experimental contexts, and this heterogeneity is likely to contribute to divergent immunotherapeutic phenotypes, including obesity-associated heterogeneity in immune checkpoint blockade (ICB) responsiveness. By integrating these layers into a source-to-sink framework, we highlight translationally relevant directions for understanding how systemic metabolites may reshape the metabolic niche of the TME and for informing more precise, context-aware, and safety-conscious metabolite-directed strategies in cancer immunotherapy.

from the album 0ºC

Naing et al. study pembrolizumab in advanced rare cancers and show that immune contexture, rather than genomic biomarkers alone, associates with clinical benefit, with responses enriched by MSI-H/TMB-H and driven by pre-existing or treatment-induced immune activation in moderately infiltrated tumors.

The tumour immune microenvironment is increasingly recognised as a critical determinant of cancer progression, prognosis, and therapeutic response, challengi...

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Read the full paper: Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas

For the past year, the Colorado Consumer Health Initiative’s Community Advisory Board (CAB) has been listening to people across Colorado about how health information is shared. We’ve heard that many people: Don’t have control over which parts of their health information are shared. Struggle to manage their information across different systems. Want providers to see the right information when they need it. Here's the background: Contexture, Colorado’s Health Information Exchange, curren...