2023 World Conference on Lung Cancer (Posters)-P1.09. SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche

P1.09. SFRP2+ CAFs Hinder Abscopal Effect from Combined Radiotherapy and Immunotherapy by Forming a Hostile Perivascular Niche - PDF(Slides)

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The study investigates the occurrence of the abscopal effect in lung cancer patients undergoing radiotherapy combined with immune checkpoint inhibitors (ICIs). The researchers used a murine lung cancer model and found that the combination therapy was effective in reducing tumor burden at the irradiated site, but not in the abscopal tumors. RNA-sequencing analysis revealed that the extracellular structure organization pathways were enriched in the abscopal tumors after combined therapy, with Sfrp2 identified as a central hub. SFRP2 expression was found in cancer-associated fibroblasts (CAFs) and increased in abscopal tumors after the combined therapy. Blockade of SFRP2, followed by combined radiotherapy and ICI, improved the infiltration and cytotoxicity of CD8 T cells, leading to regression of abscopal tumors. In vitro experiments showed that SFRP2 CAFs induced apoptosis of CD8 T cells. Spatial transcriptome analysis revealed that SFRP2 CAFs were located near vessels and surrounded by macrophages, creating an immunosuppressive perivascular niche. Lineage-tracing assays indicated that SFRP2 CAFs originated from pericytes, and IGF-1 released by irradiated tumors facilitated their transition and stimulated SFRP2 expression. The findings suggest that SFRP2 CAFs hinder the abscopal effect by inducing CD8 T cell apoptosis and creating a hostile perivascular niche in lung cancer. Targeting SFRP2 CAFs may recondition the tumor microenvironment and promote the abscopal effect.

Asset Subtitle

Zhang Yanpei

Meta Tag

Speaker Zhang Yanpei

Topic Tumor Biology: Translational Biology - IO

Keywords

abscopal effect

lung cancer

radiotherapy

immune checkpoint inhibitors

tumor burden

Sfrp2

cancer-associated fibroblasts

CD8 T cells

apoptosis

tumor microenvironment