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The mechanisms underlying exercise-induced changes in the tumor microenvironment are incompletely understood. The authors demonstrate that aerobic exercise alters intratumoral T- and myeloid-cell function and that ERK5 S496 phosphorylation is key in exercise-dependent changes in these immune cells.
The authors study the impact of wild-type or variant HER2 on the TIME using new mouse models. Surface ENPP1 on HER2Δ16 tumor cells promotes an immune-cold environment, highlighting a potential target to convert immune-cold tumors into immune-hot tumors.
The authors characterize a library of engineered chimeric cytokine receptors (CCR) in the context of CAR T-cell therapy. These CCRs hold the potential for tailoring cytokine signaling to the type of adoptive cell therapy being developed.
Many factors reduce the efficacy of CAR T-cell therapy. The authors show AXL inhibition can skew CAR T cells to a Th1 phenotype and can selectively target M2-like cells, leading to improved CAR T-cell responses in preclinical models.
A Bispecific γδ T-cell Engager Targeting EGFR Activates a Potent Vγ9Vδ2 T cell–Mediated Immune Response against EGFR-Expressing Tumors
Vγ9Vδ2 T cells have antitumor activity. The authors show EGFR-Vδ2 bispecific T-cell engagers direct Vγ9Vδ2 T-cell reactivity to EGFR-expressing tumor cells in vitro, in vivo, and ex vivo providing rationale for testing them clinically against EGFR-expressing malignancies.
Adoptive T-cell therapy is efficacious against some cancers but there are many barriers to success in solid tumors. The authors show the Synthetic Enzyme-Armed KillER (SEAKER) drug-delivery platform can overcome some of these challenges in immunocompetent hosts.
The authors show that murine Clec4A4 and human CLEC4A on conventional dendritic cells are negative immune checkpoint regulators that impair antitumor immune responses, suggesting hCLEC4A as a potential target for immune checkpoint blockade tumor immunotherapy.
CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer
The study indicates that selective expression and regulation of CCRL2 by alveolar capillary endothelial cell subsets represents an underestimated homing signal for the migration of NK cells to the lung, which has implications for tumor immunotherapy.