Immune-related signature predicts the prognosis and immunotherapy benefit in bladder cancer

Abstract

Background: There is no good prognostic model that could predict the prognosis of bladder cancer (BCa) and the benefit of immunotherapy.

Methods: Through the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a 13-mRNA immune signature from the TCGA cohort (n = 406). We validated its prognostic value and predictive value for the benefit of immunotherapy with four independent validation cohort (GSE13507 [n = 256], GSE31684 [n = 93], GSE32894 [n = 308], and IMvigor210 cohort [n = 298]).

Results: Our results indicating that high-risk group with higher inhibitory immune cell infiltration (regulatory T cells [Tregs] and macrophage, etc), higher expression of immune checkpoints, and more T cell suppressive pathways (transforming growth factor β [TGF-β], epithelial-mesenchymal transition [EMT], etc) were activated. Besides, the immune signature showed a good predictive value for the benefit of immunotherapy in a cohort of urothelial carcinoma patients treated with PD-L1.

Conclusions: The immune signature constructed is convenient to classify the immunotherapeutic susceptibility of patients with BCa, so as to achieve precision immunotherapy for BCa.

Keywords: bladder cancer (BCa); macrophage; programmed death ligand-1 (PD-L1); regulatory T cells (Tregs); transforming growth factor β (TGF-β); tumor microenvironment (TME).