Loss of in Myeloid Cells Promotes Tumour Progression and T Cell Infiltration in Invasive Bladder Cancer.

Background: CXCR2 is a chemokine receptor expressed in myeloid cells, including neutrophils and macrophages. Pharmacological inhibition of CXCR2 has been shown to sensitize tumours to immune checkpoint inhibitor immunotherapies in some cancer types.

Objective: To investigate the effects of loss in regulation of tumour-infiltrating myeloid cells and their relationship to lymphocytes during bladder tumorigenesis.

Methods: Urothelial pathogenesis and immune contexture was investigated in an OH-BBN model of invasive bladder cancer with deleted in myeloid cells ( ). gene alterations and expression in human muscle invasive bladder cancer were analysed in The Cancer Genome Atlas.

Results: Urothelial tumour pathogenesis was significantly increased upon deletion compared to mice. This was associated with a suppression of myeloid cell infiltration in -deleted bladders shortly after the carcinogen induction. Interestingly, following a transient increase of macrophages at the outset of tumour formation, an increase in T cell infiltration was observed in -deleted tumours. The increased tumour burden in the -deleted bladder was largely independent of T cells and the status of immune suppression. The -deleted mouse model reflected the low mRNA range in human bladder cancer, which showed poor overall survival.

Conclusions: In contrast to previous reports of increased CXCR2 signalling associated with disease progression and poor prognosis, CXCR2 was protective against bladder cancer during tumour initiation. This is likely due to a suppression of acute inflammation. The strategy for sensitizing checkpoint immunotherapy by CXCR2 inhibition in bladder cancer may benefit from an examination of immune suppressive status.