Carbonic Anhydrase Inhibitor Acetazolamide Enhances CHOP Treatment Response and Stimulates Effector T-Cell Infiltration in A20/BalbC Murine B-Cell Lymphoma.

International Journal of Molecular Sciences
Gábor MéhesGyörgy Trencsényi

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-assoc...Continue Reading

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Methods Mentioned

BETA
environmental stress

Software Mentioned

BrainCad
Leica LASV4

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