Single-cell Landscape reveals the Immune Heterogeneity of Bone Marrow Involvement in Peripheral T-cell lymphoma

Evaluation of Bone marrow involvement (BMI) in Peripheral T-cell lymphoma (PTCL) patients is essential for determining the prognosis. However, the tumor microenvironment of bone marrow in PTCL patients remains unclear. We collected 11 fresh bone marrow samples from the patients with BMI and performed the scRNA-seq analysis. Based on the scRNA-seq profiles, we found the immune heterogeneity and the genetic variation at single-cell resolution in the different progress of PTCL. For the immune heterogeneity, the main heterogeneity is in the lymphocytes. There were more effector T cells in AITL compared with PTCL-NOS. We also found more inflammatory response and exhausted lymphocyte cells enriched in AITL compare PTCL-NOS. The immune heterogeneity in AITL was also associated with the prognostic relevance after treatment. In the response group with anti-CD30 tharapy, more specific TCR-T cells enriched in the patients with better response. Further analysis showed the RHOA mutation leading the neoantigen was observed. In the response group with Chidamide treatment, the patients with more CD4 regulate cells could get better response. In the progressed group, the early sign of transformation from T cells to B-like cells was found in the progressed group developed into the diffuse large B cell lymphoma. Moreover, the AITL patients with lymphoma-associated hemophagocytic syndrome contain the precursor exhausted cells with the copy number variation in Chr5. Overall, this study is the first single cell landscape depicting the tumor microenvironment heterogeneity in the bone marrow of PTCL. Moreover, it is innovative in applying the scRNA-seq technology to investigate the immune heterogeneity and the genetic variation at single-cell resolution for the different progress in the treatment of AITL.