Cancer-associated fibroblasts (CAFs) are heterogeneous and ubiquitous stromal cells within the tumor microenvironment (TME). Numerous CAF types have been described, typically using single-cell technologies such as single-cell RNA sequencing. There is no general classification system for CAFs, hampering their study and therapeutic targeting. We propose...

Watson et al. show that multiple modes of therapy-induced glioblastoma regression are associated with fibrosis, which promotes tumor cell survival. Using multi-omics analyses, they identify the signaling pathways related to immunotherapy-associated fibrosis and show that inhibition of this response improves survival in preclinical trials.

Lad et al. demonstrate that calvarial bone marrow supplies the glioblastoma microenvironment with antigen-presenting myeloid cells, including immature neutrophils that polarize into a “hybrid” dendritic-like phenotype. These findings convey the skull marrow as a physiologically relevant and thus clinically targetable immune component of CNS malignancies.

Stratification strategies for chemotherapy plus anti-PD-1 treatment in advanced NSCLC are critically demanded. Xu et al. develop an integrated ctDNA-based stratification strategy based on a phase 3 RCT to distinguish patients benefiting from the addition of PD-1 inhibitor and propose a potential individualized therapeutic mode for patients with advanced...

Combination immunotherapy improves outcomes in metastatic melanoma, but the underlying mechanisms remain unclear. In this issue of Cancer Cell, Wang et al. report dynamics and transcriptional states of CD8+ T cell clones over time in patients treated with anti-PD-1, anti-CTLA-4, or a combination of the two. These findings have important implications...

Liu et al. show that interneuron lineage progenitor-like states, emulating spatial niches of human brain development, present a distinct vulnerability and highlight CDK6 as a promising clinically actionable target in H3G34-mutant diffuse hemispheric glioma (DHG-H3G34).