Single cell sequencing of bone marrow infiltrating T lymphocytes in mice and humans affected by monoclonal gammopaties

Despite the extensive use of immunotherapies in hematological malignancies, the single-cell landscape of tumor infiltrating lymphocytes (TILs) in these patients lags behind what has been accomplished in solid tumors. One such example is multiple myeloma (MM), an incurable plasma cell malignancy for which treatment is being redefined by immunotherapies, while single-cell studies of TILs are scarce and the phenotype of tumor-reactive T cells remains unknown. Here we aimed at defining the phenotype of tumor-reactive T cells throughout myelomagenesis. To this end, we performed single-cell RNA and TCR sequencing of bone marrow T cells in MM and its precursor states, both in patients and experimental mouse models of spontaneous disease progression. scRNA-seq + scTCR-seq were performed in 17 bone marrow aspirates from 3 healthy adults, 3 MGUS, 2 SMM, 9 MM patients and 8 bone marrow aspirates from 2 healthy (Ycɣ1), 3 MGUS (BIcɣ1) and 3 MM (BIcɣ1) bearing mice. NOTE FROM SUBMITTER: human raw data not uploaded due to the our current privacy concerns regarding the availability of the Fasta/q files derived from healthy cells (DNA fingerprint) of patients with disease (including the possibility to derive sensible information like HLA haplotype)