WCLC 2025 - Posters & ePosters-PT1.09.03 Dormant Tumor Maintenance and Immune Evasion in Induced Oligometastatic Lung Cancer

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This prospective study investigated the characteristics of dormant tumors and immune evasion in induced-oligometastatic lung cancer using circulating tumor DNA (ctDNA) as a diagnostic tool. Twenty-one patients with oligometastatic lung cancer, treated with systemic therapy followed by surgical resection of residual lesions containing viable tumor cells (>30%), underwent perioperative comprehensive ctDNA monitoring. Tumors were classified as dormant if preoperative ctDNA was negative and proliferative if ctDNA was positive. Whole-exome sequencing and whole-transcriptome RNA sequencing were performed on tumor tissues.<br /><br />Key findings revealed that dormant tumors exhibited significantly lower immunogenicity compared to proliferative tumors, characterized by fewer neoantigens and reduced neoantigen burden. Genetic alterations, such as in-frame deletions related to neoantigen genes, were less frequent in dormant tumors. Additionally, genes involved in cell division pathways were markedly downregulated, reflecting the non-proliferative status of dormant tumors.<br /><br />The dormant tumor microenvironment was more immunosuppressive, featuring elevated levels of M2 macrophages and regulatory T cells, which suppress immune effector functions. This environment likely facilitates tumor cell evasion from host immune surveillance, contributing to cancer recurrence and resistance to therapy.<br /><br />The study concludes that ctDNA-negative status identifies a unique tumor dormancy phenotype with immunosuppressive mechanisms. These insights highlight the potential of ctDNA as a novel biomarker to explore tumor dormancy and immune evasion in oligometastatic lung cancer. Future research should focus on leveraging ctDNA to uncover immunosuppressive pathways in dormant tumors and develop targeted therapies, potentially improving outcomes in lung cancer patients.<br /><br />References included recent reviews addressing cancer cell dormancy and the lifecycle of dormant cancer cells, emphasizing the clinical relevance of targeted strategies against dormant tumor states.

Asset Subtitle

Rui Fu

Meta Tag

Speaker Rui Fu

Topic Metastatic Non-small Cell Lung Cancer – Local Therapies

Keywords

oligometastatic lung cancer

circulating tumor DNA

ctDNA monitoring

tumor dormancy

immune evasion

neoantigen burden

immunosuppressive microenvironment

M2 macrophages

regulatory T cells

targeted therapies