Tumour‐associated macrophages in diffuse large B‐cell lymphoma: a study of the Osaka Lymphoma Study Group

Wada, Naoki; Zaki, Mona A A; Hori, Yumiko; Hashimoto, Koji; Tsukaguchi, Machiko; Tatsumi, Yoichi; Ishikawa, Jun; Tominaga, Nobuhiko; Sakoda, Hiroto; Take, Hironori; Tsudo, Mitsuru; Kuwayama, Maki; Morii, Eiichi; Aozasa, Katsuyuki

doi:10.1111/j.1365-2559.2011.04096.x

Cited by 92 publications

(78 citation statements)

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“…28 However, evaluation of macrophage phenotype indicated that M2 (CD163C) macrophage predict worse prognosis. 29 These studies highlight the heterogeneity of myeloid cell functions. Identification of the phenotype of myeloid cells that predict poor clinical outcome is crucial for use of these cells as predictive biomarker in personalized therapy and for development of targeted therapies to improve lymphoma treatments.…”

Section: Discussionmentioning

confidence: 99%

Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance

et al. 2015

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“…[14][15][16][17] Of the macrophages, classically activated M1 type TAM have been described as "good", acting to prevent the growth of tumor tissue, whereas the alternative M2 type TAM may have an opposite effect promoting angiogenesis and tumor development. [18][19][20] Importantly, however, studies in follicular lymphoma have demonstrated that the prognostic significance of the tumor microenvironment and especially macrophages is highly dependent on a given therapy.…”

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confidence: 99%

Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial

et al. 2014

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impact in DLBCL. [14][15][16][17] Of the macrophages, classically activated M1 type TAM have been described as "good", acting to prevent the growth of tumor tissue, whereas the alternative M2 type TAM may have an opposite effect promoting angiogenesis and tumor development. [18][19][20] Importantly, however, studies in follicular lymphoma have demonstrated that the prognostic significance of the tumor microenvironment and especially macrophages is highly dependent on a given therapy. [21][22][23] In the present study, we investigated how the combination of rituximab with chemotherapy influences non-malignant inflammatory cell-associated clinical outcome in DLBCL. Among all studied markers for macrophages, dendritic, and lymphoid cells, we found that pretreatment gene expression of a macrophage marker CD68 and immunohistochemically defined CD68+ TAM content had a positive prognostic impact on the survival of DLBCL patients treated with chemoimmunotherapy, whereas in patients treated without rituximab, CD68 + TAM content was associated with a poor outcome. Methods Patients and samplesThe screening cohort consisted of prospectively collected DLBCL patients who were less than 65 years old and had primary high-risk (age-adjusted IPI score 2-3) disease. They were treated in the Nordic phase II NLG-LBC-04 protocol with dose-dense chemoimmunotherapy followed by systemic central nervous system prophylaxis. 24 The patients in this correlative study represent a subset of patients in the main clinical trial and were selected on the basis of DLBCL histology, the availability of fresh frozen tissue for RNA extraction and exon arrays (gene expression cohort; n=38) and formalin-fixed, paraffin-embedded lymphoma tissue containing adequate material for the preparation of tissue microarrays (TMA; immunohistochemistry cohort; n=59), and the patients' consent to correlative studies. Details of the screening cohort are provided in Table 1, the Online Supplementary Material and Online Supplementary Table S1.The clinical protocol and sampling were approved by Institutional Review Boards, National Medical Agencies and Ethics Committees in Denmark, Finland, Norway and Sweden, and the trial was registered at ClinicalTrials.gov, number NCT01502982.To validate the findings, three independent retrospective series of chemoimmunotherapy-treated DLBCL patients were used. In order to confirm gene expression data, we used RNA sequencing data from 92 patients generated by the Cancer Genome Characterization Initiative (CGCI; dbGaP database applied study accession: phs000532.v3.p1) 25,26 and oligonucleotide-based microarray data from 233 DLBCL patients generated by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP; GEO dataset: GSE10846).10 Both cohorts are subsets of the original study populations treated with a R-CHOP-like regimen based on the availability of complete expression data and clinical information (Online Supplementary Table S2).In order to confirm the immunohistochemical data, an independent population-based series of ...

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“…[7][8][9][10][11][12][13] IHC can be extended to clinical practice, which makes it highly attractive as a diagnostic and prognostic tool. Nevertheless, the results published regarding the immune microenvironment in DLBCL are contradictory.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP

et al. 2014

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Tumour‐associated macrophages in diffuse large B‐cell lymphoma: a study of the Osaka Lymphoma Study Group

Abstract: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.

Cited by 92 publications

References 18 publications

Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance

Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance

Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP

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Tumour‐associated macrophages in diffuse large B‐cell lymphoma: a study of the Osaka Lymphoma Study Group

Abstract: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.

Cited by 92 publications

References 18 publications

Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/negmonocytes mediates chemotherapy resistance

Immune independent crosstalk between lymphoma and myeloid suppressor CD14+HLA-DRlow/negmonocytes mediates chemotherapy resistance

Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial

Revisiting the immune microenvironment of diffuse large B-cell lymphoma using a tissue microarray and immunohistochemistry: robust semi-automated analysis reveals CD3 and FoxP3 as potential predictors of response to R-CHOP

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Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance

Immune independent crosstalk between lymphoma and myeloid suppressor CD14⁺HLA-DR^low/negmonocytes mediates chemotherapy resistance