Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy
| Autor: | Hannah Garavaglia, Hai Huang, Allan Tsung, Anutosh Ganguly, Clifford S. Cho, Shibin Qu, M.S. Toma, Megan Beems, Ashley L Pepple, Ryan Hubbard, Amy E Felsted, Zhen Xu, Alicia A Kevelin, Tejaswi Worlikar, Joe Dib |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
tumors
Ablation Techniques Cancer Research Lung Neoplasms Lymphocyte medicine.medical_treatment Immunology Melanoma Experimental Mice 03 medical and health sciences Histotripsy Antineoplastic Agents Immunological Liver Neoplasms Experimental 0302 clinical medicine Immune system Cancer immunotherapy Antigen medicine Animals Immunology and Allergy CTLA-4 Antigen RC254-282 030304 developmental biology Clinical/Translational Cancer Immunotherapy Pharmacology 0303 health sciences business.industry Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunotherapy medicine.disease Combined Modality Therapy 3. Good health Mice Inbred C57BL Radiation therapy medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research High-Intensity Focused Ultrasound Ablation Molecular Medicine business |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | BackgroundDeveloping the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens.MethodsImmunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection.ResultsHistotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma.ConclusionsThese preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|