Molecular signatures of T cells targeting multiple myeloma

By integrating antigen specificity and the transcriptional profile of single myeloma-associated T cells using the CDR3 sequence as clone-specific barcode, we found that tumor-reactivity results in a specific gene expression state of bone marrow-resident CD8+ T cells. Non-tumor-reactive clones were either CD4+ or enriched for viral specificities, while myeloma reactive TCRs demonstrated an increased clonality within the overall lymphocyte repertoire.

We furthermore describe a subset of CD29 (ITGB1)-expressing effector-memory CD8+ T cells that is associated with response to induction immunochemotherapy. Our results demonstrate antitumor reactivity in a subset of bone marrow-resident T cells against malignant plasma cells and provide the rationale for future personalized TCR-transgenic cell therapy approaches in newly diagnosed multiple myeloma patients. More broadly, the generated resources from this project might contribute to identifying and monitoring tumor reactive T cell responses targeting hematological neoplasias.