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.