In This Issue
Cancer Discov March 1 2021 11 (3) 521-523; DOI:10.1158/2159-8290.CD-ITI2021-0102
Tumor sequencing data from patients with lung cancer from Latin America revealed that Native American ancestry significantly affected tumors' somatic mutation profiles; the observed disparities arose from germline differences rather than environmental exposures.
Apoptotic FAS–FASL signaling enabled CD8+ T cells to exert cytotoxic effects on antigen-negative “bystander” tumor cells in vivo, possibly explaining how antigen-specific chimeric antigen receptor T-cell therapies can eliminate tumors with heterogeneous antigen expression.
A new mouse model of immune checkpoint inhibitor–induced myocarditis was developed, enabling the discovery that abatacept may be useful for ameliorating this condition; this finding was supported by results from a patient case series.
Black patients with AML fared worse than white patients, a trend that held true after adjusting for socioeconomic status and molecular features, and the impact of common prognosticating mutations (e.g., those in NPM1) differed between the two groups.
Transcriptomic and DNA methylomic analyses revealed the existence of an aggressive, ductal cell–derived pancreatic ductal adenocarcinoma subgroup defined by low methylation of repetitive elements and expression of an IFN-linked transcriptional program.
Pancreatic ductal adenocarcinomas in adult genetically engineered mice could arise from either ductal or acinar cells, and tumors arising from each cell type had distinct transcriptional profiles that matched those of defined human pancreatic cancer subtypes.
Melanoma circulating tumor cells (CTC) prevented ferroptotic death by upregulating SREBF2-mediated lipogenic pathways and iron homeostatic pathways, and blocking this escape mechanism by knocking out the gene encoding transferrin hindered CTC tumor formation.
An ex vivo bioassay, ATLAS, was able to identify stimulatory and inhibitory neoantigens for the design of personalized anticancer vaccines; this assay pinpointed anti- and protumorigenic antigens, as demonstrated via in vivo experiments.
Type II RAF inhibitors provided distinct advantages over Type I RAF inhibitors when used in combination with MEK inhibitors in models with MAPK pathway alterations.
A screen for tumor cell–intrinsic suppressors of antitumor immunity identified the histone methyltransferase KDM3A, which activated the expression of EGFR to keep the tumor immune microenvironment in a non–T-cell-inflamed state.
A genetic tracing method using synthetic reporters comprised of glioblastoma subtypespecific cis-regulatory elements allowed mapping of cell states and fate transitions.
A lineage-independent, unbiased approach to characterize Hippo pathway activity and dependency identified cross-talk between the Hippo and MAPK pathways and suggested a potential therapeutic strategy for Hippodependent cancers.