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Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients

  1. Author:
    Hwang, Ilseon
    Kim, Jeong Won
    Ylaya, Kris
    Chung, Eun Joo
    Kitano, Haruhisa
    Perry,Candice
    Hanaoka, Jun
    Fukuoka, Junya
    Chung, Joon-Yong [ORCID]
    Hewitt, Stephen M [ORCID]

  2. Author Address

    Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC1500, Bethesda, MD, 20892, USA., Department of Pathology, Keimyung University Scholl of Medicine and Institute for Cancer Research, Dongsan Medical Center, Daegu, 42601, Republic of Korea., Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, Republic of Korea., Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Department of Thoracic Surgery, Vories Memorial Hospital, Shiga, 523-0806, Japan., Department of Thoracic Surgery, Shiga University of Medical Science, Otsu, 520-2192, Japan., Advanced Biomedical Computational Science, Biomedical Informatics and Data Science, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA., Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan., Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC1500, Bethesda, MD, 20892, USA. chungjo@mail.nih.gov., Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC1500, Bethesda, MD, 20892, USA. genejock@helix.nih.gov.,
    1. Year: 2020
    2. Date: Nov 23
    3. Epub Date: 2020 11 23
  2. Journal: Journal of translational medicine
    1. 18
    2. 1
    3. Pages: 443
  4. Type of Article: Article
  5. Article Number: 443
  6. ISSN: 1479-5876
  1. Abstract:

    Background: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). Methods: Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system. Results: CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratiohigh and VEGF-Chigh (M2 ratiohighVEGF-Chigh) was correlated with worse overall survival (p = 0.033). Multivariate analysis revealed that M2 ratiohigh [HR (95% CI) = 1.53 (1.01-2.33), p = 0.046] and combined M2 ratiohighVEGF-Chigh expression [HR (95% CI) = 2.01 (1.28-3.16), p = 0.003] were independent predictors of poor overall survival. Notably, we confirmed that M2 macrophages significantly enhanced the protein and mRNA expression of both VEGF-A and VEGF-C, while M1 macrophages induced only mRNA expression of VEGF-A in A549 cells. Conclusions: This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.

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External Sources

  1. View Full Text
  2. DOI: 10.1186/s12967-020-02618-z
  3. PMID: 33228719
  4. PMCID: PMC7686699
  5. View record in Web of Science®
  6. WOS: 000595676300002
  7. PII : 10.1186/s12967-020-02618-z

Library Notes

  1. Fiscal Year: FY2020-2021
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