부산대학교 도서관

The clinical management of advanced malignancies of the upper and lower urinary tract has been revolutionized with the advent of immune checkpoint blockers (ICBs). ICBs reinstate or bolster pre-existing immune responses while creating new T cell specificities. Immunogenic cancers, which tend to benefit more from immunotherapy than cold tumours, harbour tumour-specific neoantigens, often associated with a high tumour mutational burden, as well as CD8+ T cell infiltrates and ectopic lymphoid structures. The identification of beneficial non-self tumour antigens and natural adjuvants is the focus of current investigation. Moreover, growing evidence suggests that urinary or intestinal commensals, BCG and uropathogenic Escherichia coli influence long-term responses in patients with kidney or bladder cancer treated with ICBs. Bacteria infecting urothelium could be a prominent target for T follicular helper cells and B cells, linking innate and cognate CD8+ memory responses. In the urinary tract, commensal flora differ between healthy and tumoural mucosae. Although antibiotics can affect the prognosis of urinary tract malignancies, bacteria can have a major influence on cancer immunosurveillance. Beyond their role as biomarkers, immune responses against uropathogenic commensals could be harnessed for the design of future immunoadjuvants that can be advantageously combined with ICBs.
Bacteria infecting tumour cells might be a promising target for triggering antitumour immune responses. Here, the authors discuss the influence of urinary tract infections on kidney and bladder cancer immunosurveillance and consider the urobiome and the effects of antibiotics.
Key points: The immune infiltrate of the urinary tract has prognostic and predictive value in kidney and bladder cancers.Upper and lower urinary tract malignancies are not sterile.Antibiotics compromise the efficacy of immune checkpoint inhibitors.Cellular and humoral immune responses against uropathogenic Escherichia coli or BCG dictate the success of immune checkpoint inhibitors.Novel therapeutic strategies should harness the urinary or intestinal microbiota.