To delineate the role of host ATF4 in the sequence of events leading to tumor growth, we performed transcriptional profiling at the single-cell level (scRNA-seq) in larger (300 mm3) size B16F10 tumors grown in Atf4wt/wt and Atf4D/D mice. We surprisingly detected impaired CAFs activation in Atf4D/D mice, based on the expression levels of Acta2 and Pdgfrb, as one of the most commonly used CAF markers. Among our key findings, we identified the vascular CAFs (vCAFs), a spatially distinct CAF subcluster featured by the highest levels of aSMA and PDGFRb, that were reduced in Atf4D/D mice. Overall design: Large size B16F10 tumors (300 mm3) from four Atf4wt/wt and four Atf4D/D were harvested and submitted for scRNA-seq analysis.