Spatiotemporal dynamics of adoptively transferred stem-like CD8(+) T cells in the tumor microenvironment following vaccination.

Adoptive transfer of stem-like CD8+ T cells followed by intravenous vaccination prevents immune exclusion in the tumor microenvironment and reprograms tumor cells to upregulate IFN signaling programs.

• Why it matters: ACT can fail when highly differentiated T cells are suppressed by an immunosuppressive tumor microenvironment, limiting tumor control in many patients.
• What they did: The study used spatial transcriptomics to profile the tumor microenvironment after ACT with stem-like versus effector CD8+ T cells, then tested whether type I and type II IFN signaling gene programs were required for tumor control.
• The result: The stem-like ACT plus vaccination model increased pro-inflammatory macrophage infiltration, produced a protective TME transcriptomic signature overlapping with biomarkers in patients who responded to ACT, supporting transcriptional remodeling as a mechanism for improved tumor control.

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