Intratumoral macrophage phenotype and CD8 + T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma

Cornelissen, Robin; Lievense, Lysanne A.; Robertus, Jan-Lukas; Hendriks, Rudi W.; Hoogsteden, Henk C.; Hegmans, Joost P.; Aerts, Joachim

doi:10.1016/j.lungcan.2015.03.013

Cited by 23 publications

(24 citation statements)

References 36 publications

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“…The correlations between the number of TAMs or the ratio M2/TAM and the tumor progression or patients' outcomes are highly discordant. 8,17,20,34 According to our data, M2 percentage is not a significant predictor of patients' outcome but it is an immune marker that highly differentiates MPM from nonmalignant conditions, as Gr-MDSCs andto a lesser extent -Mo-MDSCs.…”

Section: Discussionmentioning

confidence: 76%

“…The amount of CD8 þ TILs has been associated with adverse or good prognosis, but in our case series, we did not detect any prognostic significance. 17,20,34 It is likely thatmore than the absolute number of CD8 þ T lymphocytestheir functional exhaustion, due to the presence of Treg cells and MDSCs, is critical in determining tumor progression and patients' outcome. 6,17 We identified high Treg cells within pleural fluid and tissue as specific biomarkers of MPM rather than of benign pleural disease or pleural MTS.…”

Section: Discussionmentioning

confidence: 99%

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Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma

Salaroglio

Kopecka

Napoli³

et al. 2019

Journal of Thoracic Oncology

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Introduction: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. Methods:We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.Results: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4 þ ) programmed death 1-positive (PD-1 þ ) (>5.2%) and CD8 þ PD-1 þ (6.4%) cells, CD4 þ lymphocyte activating 3-positive (LAG-3 þ ) (>2.8% ) and CD8 þ LAG-3 þ (>2.8%) cells, CD4 þ T cell immunoglobulin and mucin domain 3positive (TIM-3 þ ) (>2.5%), and CD8 þ TIM-3 þ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma

Salaroglio

Kopecka

Napoli³

et al. 2019

Journal of Thoracic Oncology

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“…Similar results were observed in malignant pleural mesothelioma where high amounts of CD163 C and low count of CD8 C cells were associated with local tumor outgrowth. 22 Of interest CD8 C T-cells infiltration is higher in low grade non-invasive CHS, whereas CD163 C macrophages infiltration is higher in high-grade invasive tumors. These observations seem to indicate that CHS can modulate its immune environment to promote the invasion in the soft tissues.…”

Section: Discussionmentioning

confidence: 94%

Description of the immune microenvironment of chondrosarcoma and contribution to progression

et al. 2016

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Chondrosarcoma (CHS) is a rare bone malignancy characterized by its resistance to conventional systemic and radiation therapies. Whether immunotherapy targeting immune checkpoints may be active in these tumors remains unknown. To explore the role of the immune system in this tumor, we analyzed the immune environment of chondrosarcomas both in human sample, and in a syngeneic rat model, and tested the contribution of T lymphocytes and macrophages in chondrosarcoma progression. Immunohistochemical stainings were performed on human chondrosarcoma samples and on Swarm rat chondrosarcoma (SRC) model. Selective immunodepletion assays were performed in SRC to evaluate immune population's involvement in tumor progression. In human and rat chondrosarcoma, immune infiltrates composed of lymphocytes and macrophages were identified in the peritumoral area. Immune infiltrates composition was found correlated with tumors characteristics and evolution (grade, invasiveness and size). In SRC, selective depletion of T lymphocytes resulted in an accelerated growth rates, whereas depletion of CD163 macrophages slowed down tumor progression. Splenocytes isolated from CHS-bearing SRC showed a specific cytotoxicity directed against chondrosarcoma cells (27%), which significantly decreased in CD3-depleted SRC (11%). The immune environment contributes to CHS progression in both human and animal models, suggesting that immunomodulatory approaches could be tested in bone chondrosarcoma.

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“…A major issue is that pharmacological inhibitors of EZH2 not only target the tumor cells, but also indirectly affect the tumor microenvironment. More specifically, macrophages are major modulators of the local antitumor immune response (8,9). In fact, macrophages show a wide range of activation states between the 2 M1 and M2 extremes (i.e., classically and alternatively activated macrophages), depending on stimuli produced in their microenvironment (10).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1–dependent mechanism

et al. 2019

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Intratumoral macrophage phenotype and CD8 + T lymphocytes as potential tools to predict local tumor outgrowth at the intervention site in malignant pleural mesothelioma

Cited by 23 publications

References 36 publications

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma

Description of the immune microenvironment of chondrosarcoma and contribution to progression

Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1–dependent mechanism

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