ArticlePloS one2015
Macrophage polarization reflects T cell composition of tumor microenvironment in pediatric classical Hodgkin lymphoma and has impact on survival.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 70 citations in OpenAlex.
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- Predictors of sensitivity to immune therapies in classic Hodgkin lymphoma.Blood neoplasia · 2026Review
- Aging cells, young patients: senescence in Hodgkin lymphoma.Blood advances · 2026Article
- The Hodgkin Lymphoma Microenvironment: Insights from Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- Spatial and multi-omic profiling reveals genes and pathways associated with cytotoxic lymphocyte infiltration in malignant rhabdoid tumor.Research square · 2025Article
- Tumor-associated macrophages: potential role in skeletal involvement in classic Hodgkin lymphoma.The journal of pathology. Clinical research · 2025Article
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- Spatial transcriptomics reveals prognostically LYZCancer immunology, immunotherapy : CII · 2025Article
- A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration.BJC reports · 2025Article
- Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults.Frontiers in oncology · 2025Review
- Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma.Journal of experimental & clinical cancer research : CR · 2024Article
- TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8Cancer immunology, immunotherapy : CII · 2024Article
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- Upregulation of Apolipoprotein L6 Improves Tumor Immunotherapy by Inducing Immunogenic Cell Death.Biomolecules · 2023Article
- A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases.Scientific reports · 2022Article
- Transmissible ER stress between macrophages and tumor cells configures tumor microenvironment.Cellular and molecular life sciences : CMLS · 2022Article
- Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein-Barr Virus-Associated Malignancies.Viruses · 2022Review
- Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis.International journal of molecular sciences · 2022Article
- Polarization of Macrophages in Granulomatous Cutaneous T Cell Lymphoma Granulomatous Mycosis Fungoides Microenvironment.Dermatopathology (Basel, Switzerland) · 2022Article
- Major pathways involved in macrophage polarization in cancer.Frontiers in immunology · 2022Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages have been implicated in the pathogenesis of classical Hodgkin lymphoma (cHL) and have been suggested to have a negative impact on outcome. Most studies addressing the role of macrophages in cHL have relied on identification of macrophages by generic macrophage antigens, e.g., CD68. We have therefore conducted an in situ analysis of macrophage polarization in a series of 100 pediatric cHL (pcHL) cases using double staining immunohistochemistry, combining CD68 or CD163 with pSTAT1 (M1-like) or CMAF (M2-like). M1- or M2-polarised microenvironment was defined by an excess of one population over the other (>1.5). Expression of STAT1 and LYZ genes was also evaluated by RT-qPCR. Patients <14 years and EBV+ cases displayed higher numbers of CD68+pSTAT1+ cells than older children and EBV- cases, respectively (P=0.01 and P=0.02). A cytotoxic tumor microenvironment, defined by a CD8+/FOXP3+ ratio >1.5 was associated with higher numbers of CD68+pSTAT1+ (P=0.025) and CD163+pSTAT1+ macrophages (P<0.0005). Levels of STAT1 and LYZ expression were associated with the numbers of CD68+pSTAT1+ macrophages. EBV+ cHL cases disclosed a predominant M1 polarized microenvironment similar to Th1 mediated inflammatory disorders, while EBV- cHL showed a predominant M2 polarized microenvironment closer to Th2 mediated inflammatory diseases. Better overall-survival (OS) was observed in cases with higher numbers of CD163+pSTAT1+ macrophages (P=0.02) while larger numbers of CD163+CMAF+ macrophages were associated with worse progression-free survival (PFS) (P=0.02). Predominant M1-like polarization as disclosed by CD163+pSTAT1+/CD163+CMAF+ ratio > 1.5 was associated with better OS (P= 0.037). In conclusion, macrophage polarization in pcHL correlates with prevalent local T cell response and may be influenced by the EBV-status of neoplastic cells. Besides, M1-like and M2-like macrophages displayed differential effects on outcome in pcHL.
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