CSF-1R Expression in Tumor-Associated Macrophages Is Associated With Worse Prognosis in Classical Hodgkin Lymphoma

Koh, Young Wha; Park, Chan-Sik; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

doi:10.1309/ajcpr92tddfarisu

Cited by 40 publications

(28 citation statements)

References 33 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in accordance with previous reports describing CSF1 (ligand) expression in tumour cells but the receptor, CSF1R, in the surrounding TAM populations [40]. In contrast, a recent report describes some level of CSF1R protein expression in a fraction of HRS cells in cHL [41], but more generalized CSF1R protein expression was associated with the microenvironment, using a polyclonal antibody. Also, the presence of CSF1R transcripts have been described in the HRS cells [23,24].…”

Section: Discussionsupporting

confidence: 92%

CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

et al. 2015

View full text Add to dashboard Cite

Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.

show abstract

Section: Discussionsupporting

confidence: 92%

CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Therefore, the serum Kyn/Trp ratio in patients with HL is likely to be dependent on IDO and probably not on tryptophan 2,3‐dioxygenase or IDO2, produced by macrophages/dendritic cells in the tumor microenvironment. In addition, interactions between colony stimulating factor‐1 produced by HL tumor cells and the colony stimulating factor‐1 receptor expressed by tumor‐associated macrophages/dendritic cells should play an important role for the present observations …”

Section: Discussionmentioning

confidence: 99%

Clinical significance of tryptophan catabolism in Hodgkin lymphoma

et al. 2017

View full text Add to dashboard Cite

Indoleamine 2,3‐dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly diagnosed Hodgkin lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 concentration. The IDO expression was evaluated in the patients’ affected lymph nodes. The cohort comprised 22 male and 30 female patients (age range, 15‐81 years; median, 45 years), with a 5‐year overall survival (OS) of 88.6%. The OS was significantly shorter for patients with a high Kyn/Trp ratio (OS at 5 years, 60.0% vs 92.2%), for those with stage IV disease, and for those with lymphocytopenia (<600/mm3 and/or <8% white blood cell count). The latter two parameters are components of the international prognostic score for advanced HL. In contrast, there were no significant differences in OS according to age, serum albumin, hemoglobin, sex, white blood cell count, or serum soluble CD30 (≥ or <285.6 ng/mL). Multivariate analysis using the three variables stage, lymphocytopenia, and serum Kyn/Trp ratio showed that only the latter significantly affected OS. Indoleamine 2,3‐dioxygenase 1 was produced by macrophages/dendritic cells, but not by HL tumor cells, and IDO levels determined by immunohistochemistry had a significant positive correlation with the serum Kyn/Trp ratio. In conclusion, quantification of serum Kyn and Trp is useful for predicting prognosis of individual HL patients.

show abstract

“…In 3/5 of the HL cell lines, signals for CX3CL1 were detected (ntc = no template control). as prognostic factor [175]. In HL cells, expression of CSF1R is driven by reactivation of an endogenous retroviral element [176].…”

Section: Pediatric Hematology and Oncologymentioning

confidence: 99%

Prognostic Biomarkers for Hodgkin Lymphoma

Staege

Kewitz

Bernig

et al. 2015

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

The prognosis of patients with classical Hodgkin lymphoma following chemo- and radiotherapy has been excellent during the last 4 decades. However, the development of secondary malignancies is of major concern. Therefore, the reduction of radiotherapy application is a major objective of ongoing clinical trials. De-escalation of treatment may increase the risk of relapses and thus may lead to reappearance of prognostic factors. Prognostic biomarkers might help to identify patients who are at increased risk of relapse. This review summarizes the current knowledge about potential prognostic biomarkers for patients with classical Hodgkin lymphoma.

show abstract

CSF-1R Expression in Tumor-Associated Macrophages Is Associated With Worse Prognosis in Classical Hodgkin Lymphoma

Abstract: Our data demonstrate that a high number of non-HRS cells expressing CSF-1R are correlated with an increased tumor macrophage content and worse survival.

Cited by 40 publications

References 33 publications

CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

Clinical significance of tryptophan catabolism in Hodgkin lymphoma

Prognostic Biomarkers for Hodgkin Lymphoma

Contact Info

Product

Resources

About