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Our group demonstrated that the IL-33\/ST2 pathway enhances the development of squamous cell carcinoma (SCC). Conversely, other researchers have reported that IL-33 inhibits tumour progression. In addition, the crosstalk between IL-33, cancer cells and immune cells in SCC remains unknown. The aim of this study was to investigate the effect of IL-33 on the biology of head and neck SCC lines and to evaluate the impact of IL-33 neutralisation on the T cell response in a preclinical model of SCC. First, we identified epithelial and peritumoural cells as a major local source of IL-33 in human SCC samples. Next, in vitro experiments demonstrated that the addition of IL-33 significantly increased the proliferative index, motility and invasiveness of SCC-25 cells, and downregulated <jats:italic>MYC<\/jats:italic> gene expression in SCC cell lines. Finally, IL-33 blockade significantly delayed SCC growth and led to a marked decrease in the severity of skin lesions. Importantly, anti-IL-33 monoclonal antibody therapy increase the percentage of CD4<jats:sup>+<\/jats:sup>IFN\u03b3<jats:sup>+<\/jats:sup> T cells and decreased CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells secreting IL-4 in tumour-draining lymph nodes. Together, these data suggest that the IL-33\/ST2 pathway may be involved in the crosstalk between the tumour and immune cells by modulating the phenotype of head and neck SCC and T cell activity. IL-33 neutralisation may offer a novel therapeutic strategy for SCC.<\/jats:p>","DOI":"10.1007\/s00262-024-03676-8","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T15:04:36Z","timestamp":1714057476000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interleukin 33 supports squamous cell carcinoma growth via a dual effect on tumour proliferation, migration and invasion, and T cell activation"],"prefix":"10.1007","volume":"73","author":[{"given":"Graziela","family":"Perri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa Garcia","family":"Vilas Boas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Renata Sales","family":"Nogueira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgard Jos\u00e9 Franco","family":"Mello J\u00fanior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Lucia","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin M.","family":"Posadas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cory","family":"Hogaboam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A","family":"Cavassani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Campanelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"issue":"9","key":"3676_CR1","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41568-018-0024-5","volume":"18","author":"A S\u00e1nchez-Dan\u00e9s","year":"2018","unstructured":"S\u00e1nchez-Dan\u00e9s A, Blanpain C (2018) Deciphering the cells of origin of squamous cell carcinomas. 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