Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition

Description

Datta and colleagues use single-cell sequencing to learn why blocking a protein called Axl helps some cancers but disappoints in trials, in 2026 cancer immunology research. Axl sits on myeloid cells, immune cells inside tumors that can suppress anti-cancer responses. The team grew human melanoma cells with macrophages from four healthy donors, in pairs and in three-way cultures adding dendritic cells. They then measured how each cell type's gene activity and cell-to-cell signaling changed under Axl inhibition.

Communication-mapping tools showed the drug's effects depended on which cells were present. Prior treatment of the tumor cells reshaped how myeloid cells answered Axl blockade, altering the inferred signaling patterns between cell types. Datta argues these context effects help explain the translation gap between tidy mouse experiments and mixed human trial results. Understanding myeloid responses in realistic mixtures, the authors say, should guide combination therapies built around Axl.

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Source: https://europepmc.org/article/MED/PMC13562482