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June 6, 2026Experimental & Molecular MedicineOpen Access

PLD1 and PLD2 promote an immunosuppressive tumor microenvironment via CCL19-dependent macrophage polarization and PD-L1 induction

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Authors

HLHyesung LeeSLSeong Hun LimWHWon Chan Hwang

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Overview

Randomized trial demonstrates that inhibiting PLD1 and PLD2 enhances immune activation in tumors, indicating therapeutic potential.

Key Points

  • This research investigates how PLD1 and PLD2 influence the immunosuppressive tumor microenvironment and antitumor immunity.
  • Used genetic ablation and pharmacological inhibition of PLD1 and PLD2 in a syngeneic melanoma model.
  • Analyzed macrophage polarization and T cell infiltration in response to PLD manipulation.
  • Investigated the role of CCL19 and PD-L1 in immune response modulation.
  • PLD1 and PLD2 ablation reduced M2-like TAM infiltration, increased CD8⁺ T cell presence, and enhanced T cell function.
  • PLD inhibition decreased CCL19 and PD-L1 levels, shifting the tumor microenvironment from immunosuppressive to immune-activated.
  • Loss of PLD enzymatic activity improved antitumor responses by facilitating a shift in macrophage polarization.

Cite This Study

Lee et al. (2026) studied this question.

synapsesocial.com/papers/6a23ba6871a5da9775e7610fhttps://doi.org/10.1038/s12276-026-01742-y
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