Latent effector T cells mediate immunotherapy responses in the bone marrow microenvironment

作者：Niklas Kehl, Tim Wagner, Simon Steiger, Tamara Boschert, Michael Kilian, Antonia Schach, Julius J. Michel, Kane Foster, Gabrielle M. Hernandez, Claudia Ctortecka, A Metzler, Alanna Kirschner, Arne Van der Vreken, Dominik Humer, René Onken, Sven Cuntz, Julian Zoller, Cornelius Funk, Selina Neunhäuser, Maximilian Mönnig, Bruno Schönfelder, Simon Renders, Clàudia Maldonado Torres, Lilli S. Sester, Jan H. Frenking, Franziska Werner, Wolfram Osen, Katharina Lindner, Ezgi Sen, Sabrina Schumacher, Daria Galas-Filipowicz, Evie Fitzsimons, Edward Green, Patrick Schmidt, John M. Lindner, Sebastian Uhrig, Lukas Bunse, Chain Benny, Hartmut Goldschmidt, Niels Weinhold, Stefan Fröhling, Tim Sauer, Simon Raffel, Jennifer G. Abelin, Steven A. Carr, Kwee Yong, Andreas Trumpp, Carsten Müller‐Tidow, Karsten Rippe, M. Raab, Michael Platten, Stefan B. Eichmüller, Mirco J. Friedrich · 发表于：Cancer Cell · 年份：2026 · DOI：10.1016/j.ccell.2026.07.011 · 被引用次数：1 · 研究领域：vaccines and immunoinformatics approaches、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

T cell-mediated immune surveillance is critical for cancer control, yet its role in bone marrow malignancies remains poorly understood. Here, we integrate TCR profiling, HLA immunopeptidomics, and functional screening to characterize tumor-reactive T cells in the bone marrow of patients with multiple myeloma (MM) and acute myeloid leukemia (AML). These cells are transcriptionally defined by a conserved effector program distinct from the exhausted phenotype of tumor-reactive T cells in solid cancers. Immunopeptidomic profiling reveals a partially shared antigen landscape enriched for noncanonical peptides driving convergent TCR responses. We develop TFiT (tumor-reactive features in T cells), a transcriptional classifier that identifies these cells and stratifies immunotherapy, but not chemotherapy, response across independent MM and AML cohorts, supporting its specificity for T cell-mediated tumor control. These findings reveal a latent but activatable anti-tumor T cell compartment in bone marrow malignancies and provide a framework for engaging endogenous immunity in MM and AML.