Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.

PURPOSE

The present study investigates a convenient laser-based approach to enhance dendritic cell (DC) migration and improve DC-based immunotherapy in murine models.

EXPERIMENTAL DESIGN

Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of CTLs by flow cytometry, CTL activity by in vitro CTL assay, and antitumor efficacy of DC immunization following cutaneous laser illumination in both preventive and therapeutic tumor models.

RESULTS

Laser illumination was found to significantly enlarge perforations in the perilymphatic basement membrane, disarray collagen fibers, and disrupt cell-matrix interactions in the dermis. The altered dermal tissue microenvironment permitted more efficient migration of intradermally injected DCs from the dermis to the draining lymph nodes (dLN). Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more vigorous expansion of tumor-specific IFN-γ(+)CD8(+) T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group. Laser-augmented DC immunization also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in preventive tumor models and significantly extended the survival of 4T1-resected mice in a therapeutic tumor model.

CONCLUSION

These data suggest a simple, safe, laser-based approach to significantly enhance DC-based immunotherapy.