Multiple myeloma long-term survivors exhibit sustained immune alterations decades after first-line therapy

• DOI: 10.1038/s41467-024-54543-0
• Publication Date: 2024-11-29T14:22:54Z
• Authors: Raphael Lutz; Florian Grünschläger; Malte Simon; Mohamed H. S. Awwad; Marcus Bauer; Schayan Yousefian; Niklas Beumer; Lea Jopp-Saile; Anastasia Sedlmeier; Llorenç Solé-Boldo; Bogdan Avanesyan; Dominik Vonficht; Patrick Stelmach; Georg Steinbuss; Tobias Boch; Simon Steiger; Marc-Andrea Baertsch; Nina Prokoph; Karsten Rippe; Brian G. M. Durie; Claudia Wickenhauser; Andreas Trumpp; Carsten Müller-Tidow; Daniel Hübschmann; Niels Weinhold; Marc S. Raab; Benedikt Brors; Hartmut Goldschmidt; Charles D. Imbusch; Michael Hundemer; Simon Haas
• Keywords: Cancer Research; 0303 health sciences; 03 medical and health sciences; Science; Q; Genes, Cells and Cell-Based Medicine [Topic 1]; Article

Abstract The long-term consequences of cancer and its therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization bone marrow ecosystem multiple myeloma survivors, from initial diagnosis up to 17 following a single line survival. Using comparative single-cell analyses combined with molecular, genomic, functional approaches, demonstrate that survivors exhibit pronounced alterations in their microenvironment associated impaired immunity. These immunological were frequently linked inflammatory circuit fueled by persistence or resurgence residual cells. Notably, even complete absence any detectable disease for decades, sustained changes observed, suggesting irreversible ‘immunological scarring’ caused exposure therapy. Collectively, our study provides key insights into molecular cellular myeloma, revealing both reversible compartment.