Abstract A108: Sub-clonal copy number variations between on-treatment lesions in immunotherapy resistant melanoma patients

Abstract Metastatic melanoma is a lethal form of cancer. Immunotherapy is recommended for metastatic melanoma and known to elicit beneficial response even after disease progression per RECIST. On-treatment samples hold irreplaceable predictive value. We collected needle biopsies from the metastases of different body sites from the same patient that progressed upon PD-1 treatment. Leveraging Direct Nuclear Tagmentation and RNA sequencing (DNTR- seq), we conducted single-cell genomic analyses on melanoma metastases and jointly sequenced the transcriptomes of each single melanoma cell. After 3 months of PD-1 inhibitor treatment, single-cell DNA-seq analyses on melanoma metastases from different anatomic locations displayed distinct cancer subclones evidenced by their copy number aberrations. Joint transcriptomic analyses of the dominant genomic subclones from each body site showed converging phenotypes, under the selective pressure of immunotherapy. Our preliminary analyses of on-treatment needle biopsies shed light on the challenges of treating heterogeneous tumors and underscore the pressing need to identify an ideal denominator to reach disease control. Citation Format: Muyi Yang, Solrun Kolbeinsdottir, Katarina Hammarlund, Vitali Grozman, Martin Enge, Suzanne Egyhazi-Brage, Hildur Helgadottir. Sub-clonal copy number variations between on-treatment lesions in immunotherapy resistant melanoma patients [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A108.