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Carbonic Anhydrase Inhibitor Acetazolamide Enhances CHOP Treatment Response and Stimulates Effector T-Cell Infiltration in A20/BalbC Murine B-Cell Lymphoma
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 14, p 5001 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- The inhibition of cancer-related carbonic anhydrase (CA) activity is a promising way to intensify anti-tumor responses. In vitro data suggest improved efficacy of cytotoxic drugs in combination with CA-inhibitors in several cancer types. Despite accumulating data on CA-expression, experimental or clinical studies towards B-cell lymphoma therapy are missing. We therefore decided to test the effect of the CA-inhibitor acetazolamide (AA) on the conventional CHOP treatment regimen using the A20/BalbC in vivo syngeneic mouse lymphoma model. Tumor growth characteristics, 18F-MISO-PET activity, histomorphology, cell proliferation, and T-cell immune infiltrate were determined following single or multiple dose combinations. All results point to a significant increase in the anti-tumor effect of CHOP+AA combinations compared with the untreated controls or with the single CHOP or AA treatments. CD3+ and CD8+ T-cell immune infiltrate increased 3–4 times following CHOP+AA combination compared with the classical CHOP protocol. In conclusion, CA-inhibitor AA seems to act synergistically with the anti-tumor treatment CHOP in aggressive lymphoma. Further to a cytotoxic effect, AA and other more selective blockers potentially support tumor-associated immune responses through the modification of the microenvironment. Therefore, CA-inhibitors are promising candidates as adjuvants in support of specific immunotherapies in lymphoma and other malignancies.
Details
- Language :
- English
- ISSN :
- 14220067 and 16616596
- Volume :
- 21
- Issue :
- 14
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.94198c3fcc2343aab102a2c96d246ea3
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/ijms21145001