肾细胞癌中高水平的PD-L1+和Hyal2+髓源性抑制细胞

IF 1.9 Q3 ONCOLOGY Journal of Kidney Cancer and VHL Pub Date : 2022-04-16 DOI:10.15586/jkcvhl.v9i2.208
S. Kusmartsev, Elizabeth P. Kwenda, Paul R. Dominguez-Gutierrez, P. Crispen, P. O'Malley
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引用次数: 4

摘要

肾细胞癌(RCC)患者循环中免疫抑制性骨髓细胞的数量经常增加。血液中大量的骨髓源性抑制细胞(MDSC)与免疫抑制以及癌症相关炎症有关,癌症相关炎症驱动骨髓细胞动员到肿瘤组织。在这里,我们发现来自先前未经治疗的RCC患者的外周血增加了单核细胞CD33+CD11b+MDSCs的数量,其也共表达PD-L1和膜结合酶透明质酸酶2(Hyal2)。PD-L1的表达与免疫抑制有关,而Hyal2的表达与炎症有关,因为Hyal2+髓系细胞可以降解细胞外透明质酸(HA),导致低分子量的促炎性HA片段的积累。这些发现暗示了单核细胞MDSC在肿瘤相关免疫抑制和癌症相关炎症中的潜在参与。对从同一患者的癌症组织制备的器官型肿瘤组织切片培养物的分析显示,在肿瘤间质中显著存在PD-L1+HLA-DR+巨噬细胞样或树突状细胞样抗原呈递细胞。有趣的是,基质相关的PD-L1+细胞经常具有细胞内透明质酸。总之,本研究中提供的数据表明,肿瘤募集的髓细胞和基质HA之间的相互作用可能有助于癌症的炎症和免疫耐受。
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High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma
Renal cell carcinoma (RCC) patients frequently have increased number of immunosuppressive myeloid cells in circulation. High number of myeloid-derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilization of myeloid cells to tumor tissue. Here, we show that peripheral blood from a previously untreated RCC patient has increased the number of monocytic CD33+CD11b+ MDSCs, which also co-expressed PD-L1 and membrane-bound enzyme hyaluronidase 2 (Hyal2). PD-L1 expression is associated with immune suppression, whereas expression of Hyal2 is associated with inflammation, because Hyal2+ myeloid cells can degrade the extracellular hyaluronan (HA), leading to the accumulation of pro-inflammatory HA fragments with low molecular weight. These findings implicate the potential involvement of monocytic MDSCs in both tumor-associated immune suppression and cancer-related inflammation. Analysis of organotypic tumor-tissue slice cultures prepared from cancer tissue of the same patient revealed the significant presence of PD-L1+ HLA-DR+ macrophage-like or dendritic cell-like antigen-presenting cells in tumor stroma. Interestingly, stroma-associated PD-L1+ cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal HA may contribute to the inflammation and immune tolerance in kidney cancer.
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来源期刊
自引率
6.20%
发文量
22
审稿时长
4 weeks
期刊最新文献
Novel Case of Bilateral Adrenal Tumors Confirms Pathogenicity of Previously Described c.463+4C>G Variant in the von-Hippel Lindau Gene. Identification of BCL11A, NTN5, and OGN as Diagnosis Biomarker of Papillary Renal Cell Carcinomas by Bioinformatic Analysis. Mucinous Tubular and Spindle Cell Carcinoma: Case Report and Literature Review. The Journal of Kidney Cancer wishes to inform its readers that the following article has been officially retracted. Identifying Hereditary Leiomyomatosis and Renal Cell Cancer through Unobtrusive Cutaneous Nodules: A Clinical Report.
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