Allergic inflammation and experimental skin cancer risk
The key soluble transmitters of inflammation are a group of glycoproteins secreted by inflammatory cells called cytokines. In allergic diseases such as allergic asthma, atopic eczema and allergic rhinitis, the symptoms arise from what is known as the type 2 inflammatory response (type 2 inflammation). One of the key cytokines in type 2 inflammation is interleukin-13 (IL-13), which causes, among other things, bronchoconstriction, and increased mucus secretion in allergic asthma.
The basic finding of a recently published study is that the expression of the IL-13 receptor associated with allergic inflammation protects against experimental skin cancer; the tumors formed earlier and were more abundant in the absence of IL-13R1 than in its presence. Mice were used as experimental animals in the study. Murine T cells show little expression of the IL-13 receptor and, somewhat surprisingly, the study found that IL-13 receptor deficiency led to an increase in the number of immune-suppressing regulatory T cells during the development of skin cancer.
According to the researchers, this fits well with the idea that excessive regulatory T-cell activity, by inhibiting the immune response against tumour cells, may provide ‘space’ for cancer to develop. While the exact mechanism remains unclear, it is clear that when the IL-13 receptor expression on the cell surface is absent during the development of cancer, the number of regulatory T cells increases, and the immune response is suppressed (skewed). This then may leave ‘space’ for cancer cells to grow and form tumours.
The researchers also shed new light on the relationship between inflammation and cancer.
“We made the interesting observation that IL-13 receptor deficiency leads to aberrant neovascularization in skin tumours. The abnormal accumulation of inflammatory cells after IL-13R1 deficiency strongly suggests that there is a chronic oxygen deficiency in the tumours associated with this abnormal new blood vessel formation. This potentially drives the formation of cancer,” says Professor Tero Järvinen.
“This is an interesting finding because cellular signalling via the IL-13 receptor has been considered a very specific allergy-related phenomenon. Our discovery that IL-13 signalling pathway might also potentially be very centrally involved in the regulation of cellular oxygen supply remains to be studied but might in some ways change our thinking about the role of immune defence in the fight against cancer. It would be straightforward to think that it is the IL-13 receptor that regulates the body’s immune defence (inflammatory response) against cancer,” Järvinen adds.
“However, it is possible that the IL-13 receptor regulates tumour neovascularization and that the immune response is a secondary response to the lack of oxygen that develops in the tumour,” Academy of Finland Research Fellow Ilkka Junttila continues.
Junttila and Järvinen will therefore continue to investigate the current finding at the molecular level.
“It is easy to see two new lines of research opening up in the wake of this finding: both the basic immunological effect of immune response on cancer development and the molecule-level role of IL-13R1 in it, and on the other hand the effect of the IL-13 receptor on neovascularization,” Järvinen and Junttila say.
The study was carried out at the Faculty of Medicine and Health Technology at Tampere University in Finland.
The analysis involved close collaboration between two research teams at the University, each drawing on the expertise of the other. Professor Järvinen’s research group carried out the experimental design, while Junttila’s research group carried out the parts related to the measurement of the immune response.
Tanja Salomaa*, Toini Pemmari*, Juuso Määttä*, Laura Kummola, Niklas Salonen, Martín González-Rodríguez, Liisa Parviainen, Lotta Hiihtola, Maria Vähätupa, Tero A.H. Järvinen* and Ilkka S. Junttila* IL-13Rα1 Suppresses Tumor Progression in Two-stage Skin Carcinogenesis Model by Regulating Regulatory T Cells. The Journal of Investigative Dermatology *Joint authorship
DOI: https://doi.org/10.1016/j.jid.2021.11.013
Contact:
Academy of Finland Research Fellow Ilkka Junttila
ilkka.junttila [at] tuni.fi
Professor Tero Järvinen
tero.jarvinen [at] tuni.fi
