Single‐cell landscape reveals the immune heterogeneity of bone marrow involvement in peripheral T‐cell lymphoma

• Published in: Cancer science Vol. 115; no. 8; pp. 2540 - 2552
• Main Authors: Liu, Jun, Xia, Baijing, Jiang, Xinmiao, Cao, Lixue, Xi, Zhihui, Liang, Liting, Zhang, Shaojun, Zhang, Hui, Li, Wenyu
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2024
• Subjects: Adult; Aged; angioimmunoblastic T‐cell lymphoma; Bar codes; Bone marrow; Bone Marrow - immunology; Bone Marrow - pathology; CD30 antigen; CD4 antigen; Cells; Copy number; Disease; Female; Gene expression; Genetic diversity; Genetic Heterogeneity; genetic variation; Genomics; Hemophagocytic syndrome; Humans; immune heterogeneity; Immunoregulation; Lymphocytes; Lymphocytes T; Lymphoma; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - immunology; Lymphoma, T-Cell, Peripheral - pathology; Male; Middle Aged; Morphology; Mutation; Neoantigens; peripheral T‐cell lymphoma; Polymorphism; Prognosis; Receptors, Antigen, T-Cell - genetics; rhoA GTP-Binding Protein - genetics; RhoA protein; Single-Cell Analysis; single‐cell RNA sequencing; Software; T-cell lymphoma; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; peripheral T‐cell lymphoma; genetic variation; angioimmunoblastic T‐cell lymphoma; tumor microenvironment; immune heterogeneity; single‐cell RNA sequencing
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.16227

The prognosis of patients with peripheral T‐cell lymphoma (PTCL) depends on bone marrow involvement (BMI). The bone marrow (BM) tumor microenvironment in PTCL remains unclear. We performed single‐cell RNA sequencing (scRNA‐seq) on 11 fresh BM samples from patients with BMI to reveal the associations of immune landscape and genetic variations with the prognosis of PTCL patients. Compared with PTCL not otherwise specified (NOS), angioimmunoblastic T‐cell lymphoma (AITL) had a higher number of T cells, lower number of lymphocytes, and greater inflammation. Immune heterogeneity in AITL is associated with prognosis. In particular, specific T‐cell receptor (TCR) T cells are enriched in patients with good response to anti‐CD30 therapy. We observed RhoA mutation‐associated neoantigens. Chidamide‐treated patients had a higher number of CD4+ regulatory cells and a better treatment response compared with other patients. In the nonresponder group, T‐cell enrichment progressed to secondary B‐cell enrichment and subsequently diffuse large B‐cell lymphoma. Moreover, AITL patients with lymphoma‐associated hemophagocytic syndrome had more T follicular helper (Tfh) cells with copy number variations in CHR5. To our knowledge, this study is the first to reveal the single‐cell landscape of BM microenvironment heterogeneity in PTCL patients with BMI. scRNA‐seq can be used to investigate the immune heterogeneity and genetic variations in AITL associated with prognosis. Based on single‐cell RNA sequencing (scRNA‐seq), we revealed the immune landscape and genetic variation at single‐cell resolution in peripheral T‐cell lymphoma (PTCL) with different prognoses. There were more effector T cells, inflammatory response, and exhausted lymphocyte cells enriched in angioimmunoblastic T‐cell lymphoma (AITL) compared with PTCL not otherwise specified (NOS). The immune heterogeneity in AITL was associated with prognosis.