It is unclear whether and how stromal fibroblasts adapt and contribute to varying tissue microenvironments. The authors show immune-suppressive cancer-associated fibroblasts can develop an immune-promoting chemokine profile in response to cytokines released from tumor-infiltrating T cells.

Conventional dendritic cells (cDC) are critical to antitumor immunity but may be impaired in cancer patients. The authors show that type 2 cDCs are numerically decreased and phenotypically impaired systemically by inflammatory cytokines in patients with pancreatic cancer.

Deeper understanding of CAR T-cell metabolism is needed to optimize such therapeutics. The authors identify ADA as a regulator of T-cell metabolism whose overexpression in CD19-specific and HER2-specific CAR T cells increases proliferation, cytotoxicity, and memory, and decreases exhaustion.

CD69 controls TOX expression within TDLNs and regulates differentiation of terminally differentiated CD8⁺ T cells. CD69 functional blockade boosts antitumor immunity, and when combined with anti–PD-1 therapy, enhances antitumor responses against immune-refractory melanoma.

Changes in sICOS splice variant levels correlate with clinical outcomes in treated melanoma patients. The data highlight that sICOS plays a role in immune suppression and that GM-CSF efficacy involves increasing membrane-bound ICOS and induction of dendritic cell development.

The authors show high levels of a defined set of plasma inflammatory cytokines and intratumoral terminally exhausted CD8⁺ T cells correlate with worse immunotherapy outcomes for patients with variant histology RCC, providing a foundation for future biomarker studies.

To overcome some of the limitations of scRNA-seq, including modest cohort sizes, the authors use gene networks to define cell states that can deconvole bulk RNA-seq data, demonstrating convergence with scRNA-seq data, and characterizing immunotherapy response.

γδ T cells harbor inherent anticancer activity, but how tumors subvert immunosurveillance by these cells is unclear. The authors identify a mechanism of WNT-driven immune escape from antitumor tissue-resident γδ T cells that is specific to colon cancer.