Highlights of This Issue

Abstract

Tumor-associated macrophages (TAM) initiate and maintain a chronic inflammation in malignant tumors, which promotes tumor growth and metastasis. It becomes increasingly important to monitor the quantity and distribution of TAM in human tumors as new TAM-targeted cancer immunotherapies are developed. To solve this unmet clinical need, Aghighi and colleagues developed an MR imaging test for detection of TAM in sarcomas and lymphomas using the iron supplement ferumoxytol “off label” as an MRI-detectable TAM biomarker. In a first-in-human proof-of-concept clinical trial, the authors show that tumor ferumoxytol enhancement on MR images correlates with TAM quantities on histopathology.Bezrookove and colleagues examine the role of copy number elevations in the PHIP gene in melanoma progression using fluorescence in situ hybridization in three independent cohorts. The authors demonstrate an independent prognostic role for PHIP in primary melanoma, identify molecular subtypes of melanoma in which PHIP is enriched, and show that PHIP copy number is monotonically increased in the transition from primary to nodal to distant metastatic melanoma. Taken together with prior work showing that PHIP promotes melanoma metastasis in murine models, these results demonstrate a critical role for PHIP in melanoma progression, identifying PHIP as a promising target for therapy.To date, the epigenomic underpinnings of pituitary adenomas remains largely unexplored. Here, Salomon and colleagues leverage a multiomics study design to investigate the role of epigenetic alterations among PA subtypes. Genome-wide methylation analysis reveals that each pituitary adenoma subtype displays a disease-specific DNA methylation pattern. Furthermore, integrating DNA methylation and gene expression data revealed that hypomethylation of promoter regions drive increased expression of GH1 and SSTR5 genes in GH-secreting adenomas, and POMC gene in ACTH-secreting adenomas. The study suggests that epigenetic differences among pituitary adenoma subtypes play a crucial role and could be important in diagnosis and treatment decisions.Oncolytic viruses are demonstrating increasing promise as anticancer agents, with adenovirus (Ad) -based vectors proving popular. Efficacy could be enhanced through rational refinement of the capsid to maximize sequestration in cancerous cells. To achieve this, Uusi-Kerttula and colleagues redesigned the capsid to prevent uptake via all known native infectious routes and inserted a targeting peptide highly specific to the tumor-selective αvβ6 integrin. The resultant vector, Ad5NULL-A20, demonstrated exquisitely tumor-selective infection, minimal uptake in off-target organs, and significant efficacy in a model of ovarian cancer, thus providing a promising platform for future translational immuno-oncolytic applications.