Immunogenic cell death and cross-priming are reaching the clinical immunotherapy arena
Melero I., Arina A., Murillo O., Dubrot J., Alfaro C., Pérez-Gracia J.L., Bendandi M., Hervás-Stubbs S.
Centro de Investigación Médica Aplicada, Clínica Universitaria and School of Medicine, University of Navarra, Pamplona, Spain
In this issue of Clinical Cancer Research, Saji et al. show the preclinical therapeutic efficacy of combining photodynamic therapy and intratumoral injection of dendritic cells (DC) in s.c. transplanted tumors.
The investigators have used systemic doses of a hydrophilic photosensitizer and a laser beam directed at s.c. malignant lesions implanted in mice. Once this procedure had been done, bone marrow–derived DC were injected inside the experimental tumor lesions. Tumors derived from two different cell lines have been treated with this regime, and compelling data has shown synergistic effects of the therapeutic combination for both locally treated tumor and distantly implanted lesions. Additional experiments showed that the therapeutic effects correlate with a cellular immune response against tumor antigens that includes detection of cytolytic T lymphocytes that, if adoptively transferred, protect na?¨ve recipient mice from tumor challenge.
The cellular and molecular mechanisms involved in the induction of these highly efficacious therapeutic effects have not been addressed, but are likely related to the biological phenomena of tumor antigen cross-priming and immunogenic cell death. These mechanisms are now an important focus of research in immunology, among other reasons because of their promising implications to attain synergistic combinations of radiotherapy and/or chemotherapy with immunotherapy.
The most exciting points raised by this article from the group of Edgar Engleman are the potency of the treatment on the poorly immunogenic B16 melanoma model and the feasibility of the approach for clinical translation.
CITATION Clin Cancer Res. 2006 Apr 15;12(8):2385-9