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The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia
Zi-Jun Xu1,2,3, Yu Gu2,4, Cui-Zhu Wang5
1Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
Insights
Acute myeloid leukemia (AML) shows higher M2 macrophage infiltration than other cancers. The M2 marker CD206 is a promising prognostic indicator for AML patients, outperforming traditional markers.
Area of Science:
- Immunology
- Oncology
- Computational Biology
Background:
- Hematological malignancies have unique immune microenvironments compared to solid tumors.
- Tumor-infiltrating leukocytes (TILs) play a critical role in cancer progression and immune evasion.
Purpose of the Study:
- To systematically analyze TIL distribution in hematological malignancies.
- To identify specific TIL populations associated with acute myeloid leukemia (AML).
- To evaluate the prognostic value of CD206 in AML.
Main Methods:
- Utilized the CIBERSORT computational algorithm to analyze 22 TIL populations.
- Examined over 2000 bone marrow samples from 5 hematological malignancies and healthy controls.
- Validated CD206 expression and its association with survival in independent AML cohorts and via meta-analysis.
Main Results:
- AML samples showed significantly increased M2 macrophage frequencies compared to controls and other malignancies.
- High M2 macrophage infiltration correlated with poor outcomes in AML.
- CD206 expression, a marker for M2 macrophages, was elevated in AML and predicted inferior overall survival (OS) and event-free survival (EFS).
- CD206 demonstrated superior predictive performance over established prognostic markers in AML.
Conclusions:
- M2 macrophages are preferentially enriched in the bone marrow of AML patients.
- The M2 marker CD206 serves as a novel and potent prognostic biomarker for AML.
- CD206 could aid in risk stratification and personalized treatment strategies for AML.
Abstract:
Hematological malignancies possess a distinctive immunologic microenvironment compared with solid tumors. Here, using an established computational algorithm (CIBERSORT), we systematically analyzed the overall distribution of 22 tumor-infiltrating leukocyte (TIL) populations in more than 2000 bone marrow (BM) samples from 5 major hematological malignancies and healthy controls. Focusing on significantly altered TILs in acute myeloid leukemia (AML), we found that patients with AML exhibited increased frequencies of M2 macrophages, compared to either healthy controls or the other four malignancies. High infiltration of M2 macrophages was associated with poor outcome in AML. Further analysis revealed that CD206, a M2 marker gene, could faithfully reflect variation in M2 fractions and was more highly expressed in AML than normal controls. High CD206 expression predicted inferior overall survival (OS) and event-free survival (EFS) in two independent AML cohorts. Among 175 patients with intermediate-risk cytogenetics, the survival still differed greatly between low and high CD206 expressers (OS; P < .0001; 3-year rates, 56% v 32%; EFS; P < .001; 3-year rates, 47% v 25%). When analyzed in a meta-analysis, CD206 as a continuous variable showed superior predictive performance than classical prognosticators in AML (BAALC, ERG, EVI1, MN1, and WT1). In summary, M2 macrophages are preferentially enriched in AML. The M2 marker CD206 may serve as a new prognostic marker in AML.
