Non-invasive monitoring of tumor vessel perfusion predicts immune checkpoint response
Tissue biomarkers such as cytotoxic T cell:Treg ratio, PD-1 or PD-L1 expression can predict the efficacy of immune checkpoint blockade (ICB) therapies among different cancer types. However, the invasive and unstable nature of these biomarkers makes them unsuitable for monitoring individual responses to ICB throughout a course of treatment. Xichen Zheng and colleagues ...demonstrate that increased tumor vessel perfusion is a reliable predictor of early-stage ICB responses in solid tumor models. Both anti-CTLA4 and anti-PD-1 antibodies enhanced vessel perfusion in treatment-sensitive tumors. Moreover, anti-CTLA4 therapy increased tumor vessel perfusion prior to detectable changes in tumor size, as measured by Doppler ultrasonography. Non-invasive monitoring of tumor vessels may therefore provide valuable early-stage predictions of individual ICB response, enabling timely personalization of patient treatment plans.
On the cover of JCI Insight: Initiating inflammation in the early stages of cerebral malaria
Cerebral malaria (CM) is a deadly complication of malaria infection with few therapeutic interventions. Elevated levels of the chemokine CXCL10 are implicated in CM development, but how CXCL10-mediated signaling contributes to pathogenesis is not well understood. Work led by Andrew Luster at Massachusetts General Hospital now demonstrates that an IFN-γ-dependent pathway induces CXCL10 expression from brain endothelial cells, leading to impairments in T cell migration at this crucial stage of CM development. CXCL10's role in the inflammatory cascade that precedes CM point to the the CXCL10/CXCR3 chemokine axis as a potential point of intervention for this deadly complication of malaria.