Suppression of neutrophils may also inhibit metastasis.Ĭlinically, FGFR3 is one of the most important therapeutic targets in bladder cancer, and many drugs that target FGF signalling in cancers are already available (3). While suppression of anti-tumour inflammation may increase tumorigenesis, suppression of pro-tumour neutrophils may allow re-population of T cells in the tumour thereby sensitising tumours to immune checkpoint therapy. We hypothesized that sequence of signalling from myeloid cells to T cells may lead to overall immune suppression of the tumour. Myeloid cells, such as macrophages and neutrophils, could play anti- or pro-tumour roles depending on the stages of tumour progression. However, the mechanism of immune-suppression by FGFR3 in immune-cold subtype of bladder cancer is still unclear.

Studies in our lab showed that activatinf FGFR3 mutation, frequently identified in bladder cancer, suppresses anti-tumour inflammation in the early stage of bladder tumour pathogenesis, thereby increasing overall frequency of tumorigenesis (1, 2). Recent molecular classification of muscle-invasive bladder cancer showed that FGFR3 overexpression was frequently observed in luminal-papillary subtype and non-T cell inflamed, immune cold tumours. While potentially a preferred target of immunotherapy, the response is still limited. Bladder cancer is common, and one of the most highly mutated cancers, similar to lung cancer and melanoma. They pose a challenge for therapy options, particularly for checkpoint inhibitors, which are otherwise promising in many cancer types. Immune “cold” tumours are tumours with little infiltrations of T lymphocytes and therefore immune suppressed, developed by a mechanism of evasion from immune surveillance through cancer progression (Hallmarks of Cancer). Research areas: tumour immune microenvironment, growth factor signalling, molecular pathology +++ FGF signalling in regulation of tumour immune microenvironment

Molecular pathology