Carbonic anhydrase inhibitor acetazolamide enhances chop treatment response and stimulates effector t-cell infiltration in a20/balbc murine b-cell lymphoma

Gábor Méhes, Orsolya Matolay, Lívia Beke, Marianna Czenke, Róbert Pórszász, Edit Mikó, Péter Bai, Ervin Berényi, György Trencsényi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5001
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume21
Issue number14
DOIs
Publication statusPublished - Jul 2 2020

Keywords

  • Adaptation
  • Anti-tumor immunity
  • Carbonic anhydrase
  • Chemotherapy
  • Effector T-cells
  • Lymphoma
  • PH-regulation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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