淋巴结 T 细胞淋巴瘤的深层表型分析揭示了免疫改变和治疗靶点。
Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets.
发表日期:2024 May 30
作者:
Pierre Stephan, Jimmy Perrot, Allison Voisin, Maud Barbery, Thibault Andrieu, Maxime Grimont, Julie Caramel, Mathilde Bardou, Garance Tondeur, Edoardo Missiaglia, Philippe Gaulard, François Lemmonier, Laurence De Leval, Emmanuel Bachy, Pierre Sujobert, Laurent Genestier, Alexandra Traverse-Glehen, Yenkel Grinberg-Bleyer
来源:
HAEMATOLOGICA
摘要:
尽管免疫疗法彻底改变了不同实体癌和血液癌的治疗,但由于对其引发的免疫反应缺乏了解,其对淋巴结外周 T 细胞淋巴瘤 (PTCL) 的疗效有限。为了全面表征 PTCL 的免疫肿瘤微环境 (TME),我们对 11 个血管免疫母细胞 T 细胞淋巴瘤 (AITL)、7 个 PTCL、未另行指定 (PTCL、NOS) 淋巴结样本和 10 个非肿瘤样本进行了光谱流式细胞术分析控制样品。 PTCL TME 含有较大比例的调节性 T 细胞和耗尽的 CD8 T 细胞,并且可药物免疫检查点的表达丰富。有趣的是,大多数免疫细胞表面的 CD39 表达上调,对 43 名 AITL 患者的回顾性队列进行的多重免疫荧光分析表明,T 细胞高 CD39 表达与患者不良预后之间存在显着关联。总之,我们的研究揭示了淋巴结 PTCL 的复杂 TME,确定了可靶向的免疫检查点,并强调 CD39 作为一种新的预后因素。
Whereas immunotherapies have revolutionized the treatment of different solid and hematological cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCLs) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCLs, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analyses on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCLs, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor.