Skorka Katarzyna, Wlasiuk Paulina, Karczmarczyk Agnieszka, Giannopoulos Krzysztof
Department of Experimental Haematooncology, Medical University of Lublin, 20-093 Lublin, Poland.
J Clin Med. 2021 Feb 19;10(4):867. doi: 10.3390/jcm10040867.
Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through TLRs downstream signaling, hence in the current study we provided, for the first time, a complex characterization of expression of , , , and as well as their splicing forms in two distinct compartments of the microenvironment of chronic lymphocytic leukemia (CLL): peripheral blood and bone marrow. We found correlations between and expressions in both compartments, indicating their relevant cooperation in CLL. The expression was higher in CLL patients compared to healthy volunteers (HVs) (0.1780 vs. 0.128, < 0.0001). The TLRs expression was aberrant in CLL compared to HVs. Analysis of survival curves revealed a shorter time to first treatment in the group of patients with low level of expression compared to high level of expression in bone marrow (13 months vs. 48 months, = 0.0207). We suggest that expression is differentially regulated in CLL but is similarly shared between two distinct compartments of the microenvironment.
功能性Toll样受体（TLRs）可通过激活炎性细胞因子和细胞毒性T细胞反应来调节抗肿瘤作用。然而，TLR的过度表达可能促进肿瘤进展，因为TLR诱导的炎症可能刺激癌细胞向微环境中扩散。髓样分化因子88（Myd88）通过TLRs下游信号传导参与核因子κB（NF-κB）的激活，因此在本研究中，我们首次对慢性淋巴细胞白血病（CLL）微环境的两个不同部分，即外周血和骨髓中Myd88、TLR2、TLR4、TLR9及其剪接形式的表达进行了全面表征。我们发现两个部分中Myd88和TLR9的表达之间存在相关性，表明它们在CLL中存在相关协同作用。与健康志愿者（HV）相比，CLL患者中TLR9的表达更高（0.1780对0.128，P<0.0001）。与HV相比，CLL中TLRs的表达异常。生存曲线分析显示，与骨髓中TLR9高表达组相比，TLR9低表达组患者首次治疗的时间更短（13个月对48个月，P=0.0207）。我们认为，TLR9的表达在CLL中受到差异调节，但在微环境的两个不同部分中具有相似的分布情况。
