空间转录组学分析显示 CCL17 和 CCL22 是血管免疫母细胞性 T 细胞淋巴瘤 (AITL) 中抑制性免疫微环境的可靠标志物。
Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL).
机构信息
Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127 Shanghai, China.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 300020 Tianjin, China.
出版信息
Front Biosci (Landmark Ed). 2022 Sep 29;27(9):270. doi: 10.31083/j.fbl2709270.
BACKGROUND
T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated.
METHODS
Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL.
RESULTS
Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern.
CONCLUSIONS
This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease.
背景
T 细胞淋巴瘤是一种复杂且高度侵袭性的临床病理实体，预后不良。血管免疫母细胞性 T 细胞淋巴瘤（AITL）的肿瘤免疫微环境尚未得到充分研究。
方法
在这里，据我们所知，空间转录组学首次被应用于研究 AITL。
结果
使用这种方法，我们观察到 AITL 被带有免疫抑制标记的细胞包围。CCL17 和 CCL22 是 CCR4 的主要配体，其表达上调，而自然杀伤（NK）细胞和 CD8+细胞毒性 T 淋巴细胞（CTL）标记的表达下降。通过生物信息学分析推断出 Treg 细胞与 CD4+TFH-GC 区域的共定位。空间转录组学获得的结果证实 AITL 具有抑制性免疫环境。基于 CHOP 方案（环磷酰胺、多柔比星、长春新碱加泼尼松）的化疗使该 AITL 患者获得完全缓解（CR）。然而，缓解持续时间（DoR）仍然令人担忧。
结论
这项研究表明 AITL 具有免疫抑制环境，并提示抗 CCR4 治疗可能是治疗这种致命疾病的有前途的方法。
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