An in silico model to study the impact of carbonic anhydrase IX expression on tumour growth and anti-PD-1 therapy

Research output: Contribution to journalResearch articleContributedpeer-review



Immune checkpoint inhibitors (ICIs) are revolutionary cancer treatments. However, the mechanisms behind their effectiveness are not yet fully understood. Here, we aimed to investigate the role of the pH-regulatory enzyme carbonic anhydrase IX (CAIX) in ICI success. Consequently, we developed an in silico model of the tumour microenvironment. The hybrid model consists of an agent-based model of tumour-immune cell interactions, coupled with a set of diffusion-reaction equations describing substances in the environment. It is calibrated with data from the literature, enabling the study of its qualitative behaviour. In our model, CAIX-expressing tumours acidified their neighbourhood, thereby reducing immune infiltration by 90% (p < 0.001) and resulting in a 25% increase in tumour burden (p < 0.001). Moreover, suppression of CAIX improved the response to anti-PD-1 (23% tumour reduction in CAIX knockouts and 6% in CAIX-expressing tumours, p < 0.001), independently of initial PD-L1 expression. Our simulations suggest that patients with CAIX-expressing tumours could respond favourably to combining ICIs with CAIX suppression, even in the absence of pre-treatment PD-L1 expression. Furthermore, when calibrated with tumour-type-specific data, our model could serve as a high-throughput tool for testing the effectiveness of such a combinatorial approach.


Original languageEnglish
Article number20220654
JournalJournal of the Royal Society interface
Issue number198
Publication statusPublished - 25 Jan 2023

External IDs

PubMed 36695125


Sustainable Development Goals


  • agent-based model, carbonic anhydrase IX, computational model, immune checkpoint inhibitors, immunotherapy, B7-H1 Antigen, Humans, Computer Simulation, Neoplasms/drug therapy, Tumor Microenvironment, Carbonic Anhydrase IX/metabolism