Tumor-secreted AGR2 induces dendritic cell dysfunction and impairs immunotherapy efficacy in LKB1-deficient cancer.

ABSTRACT:

Background

LKB1 (STK11)-deficient tumors exhibit an immunosuppressive microenvironment that limits the efficacy of immunotherapies such as anti-programmed cell death protein 1 (PD-1) antibodies. However, the underlying mechanisms driving immune evasion remain unclear. Dendritic cells (DCs), especially conventional DC 1 (cDC1), play a crucial role in antigen presentation and CD8⁺ T-cell activation, yet their dysfunction in LKB1-deficient tumors has not been well characterized.

Methods

Tumor-intrinsic LKB1 deficiency was modeled by subcutaneous inoculation of CRISPR/Cas9-engineered Stk11-knockout tumor cell lines into syngeneic mice. DC infiltration and function were assessed through a series of flow cytometry-based in vivo and in vitro assays, including anal

SUBMITTER: Yao Y 

PROVIDER: S-EPMC12557784 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature