Radiation induces an antitumour immune response to mouse melanoma

Abstract

Purpose: Irradiation of cancer cells can cause immunogenic death. We used mouse models to determine whether irradiation of melanoma can enhance the host antitumour immune response and function as an effective vaccination strategy, and investigated the molecular mechanisms involved in this radiation-induced response.

Materials and methods: For in vivo studies, C57BL6/J mice and the B16F0 melanoma cell line were used in a lung metastasis model, intratumoural host immune activation assays, and tumour growth delay studies. In vitro studies included a dendritic cell (DC) phagocytosis assay, detection of cell surface exposure of the protein calreticulin (CRT), and small interfering RNA (siRNA)-mediated depletion of CRT cellular levels.

Results: Irradiation of cutaneous melanomas prior to their resection resulted in more than 20-fold reduction in lung metastases after systemic challenge with untreated melanoma cells. A syngeneic vaccine derived from irradiated melanoma cells also induced adaptive immune response markers in irradiated melanoma implants. Our data indicate a trend for radiation-induced increase in melanoma cell surface exposure of CRT, which is involved in the enhanced phagocytic activity of DC against irradiated melanoma cells (VIACUC).

Conclusion: The present study suggests that neoadjuvant irradiation of cutaneous melanoma tumours prior to surgical resection can stimulate an endogenous anti-melanoma host immune response.

Keywords:

• radiation
• antitumour immunity
• melanoma
• calreticulin

Acknowledgments

Thanks to the VMC Flow Cytometry Shared Resource (P30-CA68485, DK058404). This work was also supported by R01-CA112385, R21-CA128456, R01-CA89674, R01-CA125757, CA093240-06, and the Vanderbilt-Ingram Cancer Center.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.