Tumor-Associated Macrophages and Survival in Classic Hodgkin's Lymphoma

By C. Steidl, Tang Lee, Sohrab P. Shah, Pedro Farinha, G. Han, Tarun Nayar, Allen D. Delaney, Steven J. M. Jones, J. Iqbal, D. Weisenburger and 15 more. New England Journal of Medicine, 2010

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Background Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. Methods Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. Results Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P = 0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P = 0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P = 0.008), resulting in shortened disease-specific survival (P = 0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P = 0.003 vs. P = 0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies. Conclusions An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.

Subfields: Neurology, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/4323b581051c08215249458cdd3b5dc91c3e3ca9

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Citations in the corpus

Macrophage plasticity and polarization: in vivo veritas. (2012, positive): “TAM infiltration is generally associated with poor prognosis, as shown in Hodgkin disease, glioma, cholangiocarcinoma, and breast carcinoma (87, 88).”
Macrophage Polarization in Inflammatory Diseases (2014, background): “A recent experiment showed that an increased number of TAM was strongly associated with a shortened survival in classical Hodgkin’s lymphoma patients [67].”
Tumor-Associated Macrophages as Treatment Targets in Oncology (2017, background): “Steidl et al.(66) (2010) Classic Hodgkin lymphoma ABVD* CD68 >25–50% positive cells Negatively correlated with DSS (P = 0.”
International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “, 2000), and its significant correlation with the number of tumorassociated macrophages, which have been associated with enhanced malignancy and poor prognosis in different human tumors (Steidl et al., 2010).”
Macrophages in Tumor Microenvironments and the Progression of Tumors (2012, background): “Accumulating studies have demonstrated that the density of TAMs is associated with a poor prognosis, suggesting macrophages as a target for clinical therapy [104–107].”
The polarization of immune cells in the tumour environment by TGFβ (2010, background): “The mass of most solid tumours is made up of a large number of macrophages and, in general, high numbers of tumour-associated macrophages (TAMs) correlate with poor cancer prognosis; however, depending on the type and environment of the tumour, TAMs may also have antitumour activit”
Cancer stem cells: an evolving concept (2012, background): “This facilitates their engraftment with human cells but also provides a system that lacks many elements that are now thought to substantially influence tumour growt”
Therapeutic siRNA silencing in inflammatory monocytes (2011, background): “, and the number of such macrophages in patients with lymphoma inversely correlates with the length of their surviva”