Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity.

ABSTRACT:

Background

Tumor-associated macrophages (TAMs) are key drivers of the immunosuppressive tumor microenvironment (TME), thereby limiting the efficacy of immune checkpoint inhibitors (ICIs). However, the underlying mechanisms remain unclear.

Methods

Both genetic (Akr1b3 knockout) and pharmacologic (epalrestat) approaches were employed to examine the impact of Aldo-keto reductase family 1 member B1 (AKR1B1) inhibition on TAMs and T-cell function in vitro and in vivo. Mechanistic insights were obtained through RNA sequencing, flow cytometry, immunofluorescence staining, and co-culture assays. To assess therapeutic relevance, 4T1 breast cancer and LLC lung carcinoma mouse models were used to evaluate the effects of epalrestat on tumor growth, immune infiltration, and T-cell respon

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12853464 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature