Two shots of one hare
The development and growth of a tumor often occurs in spite of a normally functioning immune system capable of recognizing and killing cancer cells. Tumors create a favorable environment for growth and protection from immune cells by capturing certain elements of the immune system. In particular, cancer cells "recruit" immune cell assistants, the so-called tumor-dependent macrophages (tumour-associated macrophages, TAM), and regulatory T lymphocytes (Treg) to protect against immune attack.
Targeted inhibition of TAM by blocking colony-stimulating factor 1 (CSF1) reduces tumor growth in mouse models. Clinical trials of inhibitors targeting TAM are continuing, but it is already clear that the results in humans are not as good as expected. The lack of understanding of exactly how tumour progression is promoted THERE potentially limits the therapeutic value of these inhibitors.
Suppression of Treg action in mice by inactivating the PI3K-delta enzyme protects against a number of tumors. Idelalisib is a PI3K–delta inhibitor, it is approved by the FDA for the treatment of chronic lymphocytic leukemia and non-Hodgkin's lymphoma, but its potential for the treatment of solid tumors in humans has yet to be proven.
In this study, David Gyori and his colleagues from the Babraham Institute (UK) created a mouse model of colorectal cancer to investigate the interaction of TAM and Treg. They demonstrated the ability of each cell type to compensate for the effects of the loss of the other and thus protect the tumor from the immune system.
However, the combined inhibition of TAM and Tged significantly suppressed tumor growth. Half of the mice had a complete regression of cancer.
These results provide a compelling rationale for in-depth study of the clinical value of combination therapy targeting the CSF1 receptor and the PI3K-delta enzyme.
Article by D. Gyori et al. Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy is published in the journal JCI Insight.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Babraham Institute: Breaking through a tumour's defences.