Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death.
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.
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
Jianzhong
J
Qin
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.|Creticos Cancer Center, Advocate Illinois Masonic Medical Center, Chicago, IL, USA.
Nicholas
N
Kunda
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
Guilin
G
Qiao
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.|Creticos Cancer Center, Advocate Illinois Masonic Medical Center, Chicago, IL, USA.
Jed F
JF
Calata
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.|Creticos Cancer Center, Advocate Illinois Masonic Medical Center, Chicago, IL, USA.
Krunal
K
Pardiwala
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.
Bellur S
BS
Prabhakar
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.|Creticos Cancer Center, Advocate Illinois Masonic Medical Center, Chicago, IL, USA.|Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA.
Ajay V
AV
Maker
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D037282:Calreticulin / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D012395:Rose Bengal / Q000494:pharmacology*
D000970:Antineoplastic Agents; D037282:Calreticulin; D024243:HMGB1 Protein; D018841:HSP90 Heat-Shock Proteins; D012395:Rose Bengal