巨核细胞
促炎细胞因子
淋巴瘤
脾脏
骨髓
血小板
癌症研究
肿瘤微环境
淋巴结
生物
细胞因子
免疫学
免疫系统
造血
炎症
干细胞
遗传学
作者
Amanda E. Au,Jason Corbin,Marion Lebois,Pradnya Gangatirkar,Fatme Yassinson,Stephanie R. Hyslop,Ping Cannon,Kylie D. Mason,Connie S N Li-Wai-Suen,Alexandra L. Garnham,Diane Moujalled,Luisa Cimmino,Warren S. Alexander,Emma C. Josefsson
出处
期刊:Blood Advances
[American Society of Hematology]
日期:2022-09-08
标识
DOI:10.1182/bloodadvances.2022007849
摘要
Platelets have been shown to enhance the survival of lymphoma cell lines, but it is unclear if they play a role in lymphoma. Here we investigate a potential role for platelets and/or megakaryocytes in Eµ-myc lymphoma progression. Eµ-myc tumour cells were transplanted into recipient wild-type control mice, Mpl-/-, or TpoTg mice, which exhibit normal, low and high platelet and megakaryocyte counts, respectively. Transplanted TpoTg mice exhibited enhanced lymphoma progression with increased WBC counts, spleen and lymph node weights and enhanced liver infiltration when compared to wild-type. Conversely, tumour bearing Mpl-/- mice presented with reduced WBC counts, lymph node weights and less liver infiltration when compared to wild-type. Utilizing a Mpl-deficient thrombocytopenic immunocompromised mouse model, our results were confirmed with the human NHL GRANTA cell line. While we found that platelets and platelet released molecules supported Eµ-myc tumour cell survival in vitro, pharmacological inhibition of platelet function or anticoagulation in Eµ-myc transplanted wild-type mice did not improve disease outcome. Furthermore, transient platelet depletion or sustained Bcl-xL dependent thrombocytopenia did not alter lymphoma progression. Cytokine analysis of the bone marrow fluid microenvironment revealed increased levels of the proinflammatory molecule interleukin (IL)-1 in TpoTg mice, whereas levels were lowered in Mpl-/- mice. Moreover, RNA sequencing of blood-resident Eµ-myclymphoma cells from TpoTgand wild-type mice after tumour transplant revealed upregulation of hallmark gene sets associated with inflammatory response in TpoTg mice. We propose that a pro-inflammatory microenvironment in TpoTgmice promoted lymphoma progression.
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