Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death Dis 2017 Feb 02;8(2):e2584
Date
02/06/2017Pubmed ID
28151483Pubmed Central ID
PMC5386459DOI
10.1038/cddis.2016.473Scopus ID
2-s2.0-85011660525 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell surface, a decrease in intracellular ATP, and the release of HMGB1. To confirm the ICD phenotype, we vaccinated immunocompetent animals with syngeneic colon cancer cells treated with RB. RB-treated tumors served as a vaccine against subsequent challenge with the same CT26 colon cancer tumor cells, and vaccination with in vitro RB-treated cells resulted in slower tumor growth following inoculation with colon cancer cells, but not with syngeneic non-CT26 cancer cells, suggesting a specific antitumor immune response. In conclusion, RB serves as an inducer of ICD that contributes to enhanced specific antitumor immunity in colorectal cancer.
Author List
Qin J, Kunda N, Qiao G, Calata JF, Pardiwala K, Prabhakar BS, Maker AVAuthor
Jed Calata MD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Apoptosis
Calreticulin
Cell Death
Cell Line, Tumor
Colonic Neoplasms
HCT116 Cells
HMGB1 Protein
HSP90 Heat-Shock Proteins
HT29 Cells
Humans
Mice
Mice, Inbred BALB C
Necrosis
Rose Bengal
