Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Male 0301 basic medicine Mice, Inbred BALB C CD47 Antigen Neoplasms, Experimental Cancer Vaccines Immunophenotyping 3. Good health Mice, Inbred C57BL Thrombospondin 1 Mice 03 medical and health sciences 0302 clinical medicine Photochemotherapy Neoplastic Stem Cells Animals Tumor Escape Signal Transduction
DOI: 10.1074/jbc.m114.624965 Publication Date: 2015-02-21T03:16:06Z
ABSTRACT
Like most of the strategies for cancer immunotherapy, photodynamic therapy-mediated vaccination has shown poor clinical outcomes in application. The aim of this study is to offer a glimpse at the mechanisms that are responsible for the failure based on cancer immuno-editing theory and to search for a positive solution. In this study we found that tumor cells were able to adapt themselves to the immune pressure exerted by vaccination. The survived tumor cells exhibited enhanced tumorigenic and stem-like phenotypes as well as undermined immunogenicity. Viewed as a whole, immune-selected tumor cells showed more malignant characteristics and the ability of immune escape, which might contribute to the eventual relapse. Thrombospondin-1 signaling via CD47 helped prevent tumor cells from becoming stem-like and rendered them vulnerable to immune attack. These findings prove that the TSP-1/CD47/SIRP-α signal axis is important to the evolution of tumor cells in the microenvironment of immunotherapy and identify thrombospondin-1 as a key signal with therapeutic benefits in overcoming long term relapse, providing new evidence for the clinical promise of cancer vaccination.
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