# Galangin-loaded biomimetic dendritic cells membrane nanovaccine reprograms the ovarian cancer microenvironment via Stat3/IDO1/AhR axis to boost immunotherapy

## TL;DR

A new nanovaccine using galangin and dendritic cell membranes improves ovarian cancer immunotherapy by boosting immune responses and altering the tumor environment.

## Contribution

The novel GA-NPs@DCV nanovaccine combines galangin with dendritic cell membranes to enhance antigen presentation and target the Stat3/IDO1/AhR axis in ovarian cancer.

## Key findings

- GA-NPs@DCV enhances CD8+ and CD8+ IFN-γ+ T cell proliferation in mice.
- The nanovaccine inhibits tumor growth and prevents recurrence by modulating the tumor microenvironment.
- GA-NPs@DCV promotes tissue-resident memory T cells for long-term immunity against ovarian cancer.

## Abstract

Ovarian cancer, a highly lethal gynecological malignancy with high recurrence rates and low survival, poses significant treatment challenges. While immunotherapy, particularly dendritic cell (DC) vaccines, boosts immune responses, its clinical efficacy is limited by poor antigen presentation and weak lymph node targeting. To address this, we develop a novel biomimetic nanovaccine (GA-NPs@DCV) using cell membrane-coated nanoparticles that incorporate the natural anti-tumor agent galangin (GA) and ovarian tumor-associated antigens (TAAs). GA-NPs@DCV features the antigen-presenting functions of DCs and utilizes GA to induce tumor immunogenic cell death (ICD), which not only endows the vaccine with abundantly processed specific TAAs, but also ensures robust homing capability to lymph nodes and the tumor microenvironment. Interestingly, in OT-I/OT-II transgenic mice, GA-NPs@DCV enhances the proliferation of CD8+ and CD8+ IFN-γ+ cells to activate potent immune responses. Furthermore, a nano-DC vaccine carrying distinct antigens (NPs@DCV) not only inhibits tumor growth and activates systemic immune responses, but also effectively prevents tumor recurrence. Importantly, GA-NPs@DCV exerts potent anti-ovarian cancer effects by promoting immune activation, inhibiting immune evasion through the Stat3/IDO1/AhR signaling axis, and remodeling tumor immune microenvironment via regulation of the tryptophan metabolic pathway. Notably, GA-NPs@DCV also promotes the generation of tissue-resident memory T cells (TRM, CD8+CD103+ cells) within tumor tissue, effectively inducing long-term protective immunity. Overall, these findings identify GA-NPs@DCV as an effective personalized nanovaccine that can simultaneously deliver tumor antigens and the Stat3 inhibitor GA to the tumor microenvironment to exert potent antitumor effects, providing a promising immunotherapeutic strategy for ovarian cancer.

Image 1

•Galangin (GA), as a Stat3 inhibitor, exhibits anti-ovarian cancer (OC) activity.•GA-NPs@DCV is constructed to mimic APCs and home to lymph nodes and tumors.•GA-NPs@DCV enhances antigen-specific CTL responses to boost anti-OC immunotherapy.•GA-NPs@DCV targets Stat3/IDO1/AhR axis to remodel tumor immune microenvironment.•GA-NPs@DCV promotes the generation of TRM for long-term protection against OC.

Galangin (GA), as a Stat3 inhibitor, exhibits anti-ovarian cancer (OC) activity.

GA-NPs@DCV is constructed to mimic APCs and home to lymph nodes and tumors.

GA-NPs@DCV enhances antigen-specific CTL responses to boost anti-OC immunotherapy.

GA-NPs@DCV targets Stat3/IDO1/AhR axis to remodel tumor immune microenvironment.

GA-NPs@DCV promotes the generation of TRM for long-term protection against OC.