WCLC 2025 - Posters & ePosters-P3.09.04 Macrophage CD38 Expression as a Predictive Biomarker for the Abscopal Effect in Lung Cancer Undergoing Radiotherapy-Immune Therapy

P3.09.04 Macrophage CD38 Expression as a Predictive Biomarker for the Abscopal Effect in Lung Cancer Undergoing Radiotherapy-Immune Therapy

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This study investigates macrophage CD38 expression as a predictive biomarker for the abscopal effect in lung cancer patients undergoing combined radiotherapy and immunotherapy. The abscopal effect—tumor regression at sites distant from irradiation—is rare but clinically important, highlighting the need for reliable biomarkers to identify and potentially increase its incidence.<br /><br />Key findings show that radiotherapy elevates CD38 expression in macrophages within abscopal tumors, while blocking CD38 enhances T cell infiltration and improves tumor regression. Experiments using CD38 inhibitors or CD38 knockout mice demonstrated significantly improved control of abscopal tumors post-radiotherapy. Mechanistically, serum extracellular vesicles (EVs) released after radiotherapy promote macrophage CD38 expression via STING activation and mitophagy pathways.<br /><br />Clinically, macrophage CD38 levels in peripheral blood correlate with patient response: CD38 rises in those with progressive disease and declines in responders, underscoring its role as both a predictive biomarker and a therapeutic target. The study emphasizes the potential of targeting CD38 to improve outcomes in lung cancer patients receiving radiotherapy-immunotherapy.<br /><br />Future research aims to elucidate how tumor-derived EVs drive macrophage CD38 upregulation and mitophagy, with the goal of developing therapeutic strategies targeting CD38 to enhance anti-tumor immune responses and increase the abscopal effect frequency.<br /><br />In summary, high macrophage CD38 expression predicts poor response to combined radiotherapy and immunotherapy in lung cancer. Modulation of CD38, through inhibition or genetic knockout, improves immune infiltration and tumor control, offering a promising approach to leverage the abscopal effect and improve patient outcomes. This work highlights macrophage CD38 as an actionable biomarker and therapeutic target to optimize multimodal cancer therapy.

Asset Subtitle

Yuanjun Wu

Meta Tag

Speaker Yuanjun Wu

Topic Metastatic Non-small Cell Lung Cancer – Local Therapies

Keywords

macrophage CD38

abscopal effect

lung cancer

radiotherapy

immunotherapy

biomarker

extracellular vesicles

STING activation

mitophagy

T cell infiltration