Discovery of a T cell proliferation-associated regulator signature correlates with prognosis risk and immunotherapy response in bladder cancer.

Abstract

Background: The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa).

Methods: T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort.

Results: BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31 T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort).

Conclusions: Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.