Sant'Ana Alexia N, Dias Camila K, Nunes Vitória B S, Farias Mariela G, Alegretti Ana P, Portela Pâmela, Calvache Ebellins T, Meirelles Maria F, Daudt Liane E, Michalowski Mariana B, Paz Alessandra A, Figueiró Fabrício
Laboratório de Imunobioquímica do Câncer, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, 90035-003, Brazil.
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, 90035-003, Brazil.
Immunol Res. 2024 Dec 14;73(1):11. doi: 10.1007/s12026-024-09558-6.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population that acts on both innate and adaptive immunity, fostering immune escape in tumors and contributing to cancer progression. Despite the lack of definitive markers for immunophenotyping MDSCs, particularly the polymorphonuclear (PMN-MDSC) subset, these cells seem to play a crucial role in acute myeloid leukemia (AML) patients' prognosis. Additionally, the maturation stage of MDSCs remains a subject of debate and is largely unknown within the AML context. In this study, we conducted a retrospective analysis of flow cytometry immunophenotyping data obtained at the diagnosis of AML patients. We explored how the enrichment of neutrophil maturation stages, the frequency of PMN-MDSC-like cells and monocytic MDSC-like population (M-MDSC-like), and the ratios of MDSC-like cells to T lymphocytes correlate with relevant prognostic indicators. Our findings revealed that CD45CD33HLA-DRCD36 PMN-MDSC-like cells and mature CD13CD11bCD10 neutrophils correlate poor survival in AML patients. Furthermore, PMN-MDSC-like cells, and their ratio to T lymphocytes, are elevated in patients with adverse-risk stratification. Similarly, the M-MDSC-like population is increased in FLT3-ITD mutation carrier patients. Notably, we observed confirmational evidence of CD36 relevance in the AML context, which has emerged recently as a potential marker for PMN-MDSCs. Our study highlights significant findings associating increased MDSC-like subsets and poor prognostic factors in AML.
髓系来源的抑制细胞（MDSCs）是一类异质性细胞群体，作用于固有免疫和适应性免疫，促进肿瘤中的免疫逃逸并推动癌症进展。尽管缺乏用于MDSCs免疫表型分析的明确标志物，尤其是多形核（PMN-MDSC）亚群，但这些细胞似乎在急性髓系白血病（AML）患者的预后中起着关键作用。此外，MDSCs的成熟阶段仍是一个有争议的话题，在AML背景下很大程度上尚不明确。在本研究中，我们对AML患者诊断时获得的流式细胞术免疫表型数据进行了回顾性分析。我们探讨了中性粒细胞成熟阶段的富集情况、PMN-MDSC样细胞和单核细胞MDSC样群体（M-MDSC样）的频率，以及MDSC样细胞与T淋巴细胞的比例如何与相关预后指标相关。我们的研究结果显示，CD45CD33HLA-DRCD36 PMN-MDSC样细胞和成熟的CD13CD11bCD10中性粒细胞与AML患者的不良生存相关。此外，在具有不良风险分层的患者中，PMN-MDSC样细胞及其与T淋巴细胞的比例升高。同样，在FLT3-ITD突变携带者患者中，M-MDSC样群体增加。值得注意的是，我们观察到了CD36在AML背景下相关性的确证证据，CD36最近已成为PMN-MDSCs的一个潜在标志物。我们的研究突出了AML中MDSC样亚群增加与不良预后因素相关的重要发现。
