肿瘤细胞治疗研究
英文原题：Single-cell landscape reveals the immune heterogeneity of bone marrow involvement in peripheral T-cell lymphoma.
外周 T 细胞淋巴瘤（PTCL）患者的预后取决于骨髓受累（BMI）。
外周 T 细胞淋巴瘤（PTCL）患者的预后取决于是否累及骨髓（BMI），但 PTCL 骨髓（BM）肿瘤微环境尚不清楚。我们对 11 份来自骨髓受累患者的新鲜 BM 样本进行单细胞 RNA 测序（scRNA-seq），以揭示免疫图谱和遗传变异与 PTCL 患者预后的关联。与未特指型 PTCL（NOS）相比，血管免疫母细胞性 T 细胞淋巴瘤（AITL）中 T 细胞数量更多、淋巴细胞总数较少，炎症程度更高。AITL 的免疫异质性与预后相关。尤其是，抗 CD30 治疗反应良好的患者中富集了特定 T 细胞受体（TCR）T 细胞。我们观察到与 RhoA 突变相关的新抗原。与其他患者相比，接受西达本胺治疗的患者 CD4+ 调节细胞数量更多，治疗反应更好。无应答者中，T 细胞富集随后发展为继发性 B 细胞富集，继而进展为弥漫大 B 细胞淋巴瘤。此外，伴淋巴瘤相关噬血细胞综合征的 AITL 患者中，具有 CHR5 拷贝数变异的滤泡辅助性 T（Tfh）细胞更多。据我们所知，这是首项揭示 PTCL 骨髓受累患者骨髓微环境异质性单细胞图谱的研究。scRNA-seq 可用于研究与预后相关的 AITL 免疫异质性和遗传变异。
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.
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