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FLT3L-secreting cDC1 in situ vaccination enhances antitumor immunity and synergizes with PD-1 blockade in murine non-small cell lung cancer.


ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) frequently evades immune surveillance through defective antigen presentation and a suppressive tumor microenvironment (TME), limiting the efficacy of immune checkpoint blockade (ICB). Conventional type 1 dendritic cells (cDC1s) are essential for initiating antitumor CD8+ T-cell responses; however, their abundance and function are often diminished in NSCLC, contributing to poor outcomes and resistance to immunotherapy. We hypothesized that in situ vaccination (ISV) using gene-modified cDC1s engineered to secrete FMS-like tyrosine kinase 3 ligand (FLT3L) would enhance cDC1 function within the TME, promote antitumor immunity, and improve responses to ICB.

Methods

Syngeneic murine models of NSCLC (KrasG12D/P5

SUBMITTER: Abascal J 

PROVIDER: S-EPMC13311619 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature