Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study

Murthy, Vivek; Katzman, Daniel; Tsay, J.J.; Bessich, Jamie L.; Michaud, Gaëtane; Rafeq, Samaan; Minehart, Janna; Mangalick, K.; Lafaille, Maria A. Curotto de; Goparaju, Chandra; Pass, Harvey I.; Sterman, Daniel H.

doi:10.1016/j.lungcan.2019.08.008

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…In contrast to standard immunohistochemistry, flow cytometry enables the simultaneous comprehensive analysis of many immunomodulatory markers in a single-cell population. The usefulness of this technique in the assessment of LNs in NSCLC patients has been confirmed by other authors [20,21]. For the first time, we detected CSCs and also MTCs, with the expression of molecules capable of modulation of the immune response, in LNs and PB of lung cancer patients.…”

Section: Discussionsupporting

confidence: 80%

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Raniszewska

Kwiecień

Sokołowski

et al. 2020

Cancers

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Over the past decade, immune checkpoint inhibitors have revolutionized the treatment of non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from PD-(L)1 blockade, yet, the PD-L1 tumor cell expression is the only approved biomarker, and other biomarkers have been investigated. In the present study, we analyzed the presence of immunomodulatory molecules: PD-L1, CD47, CD73, Fas, and FasL on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph nodes (LNs) aspirates and refer it to the lymphocyte subpopulation in peripheral blood (PB). PB samples and LNs aspirates obtained during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA) procedure of 20 patients at different stages of NSCLC. The cells were analyzed by multiparameter flow cytometry. We reported the higher frequency of MTCs and CSCs expressing the investigated immunomodulating molecules in metastatic LNs than in nonmetastatic. The expression of CD47 and PD-L1 was significantly higher on CSCs than on MTCs. Among the lymphocyte subpopulation in PB, we observed a higher frequency of PD-1+ CD8 T cells and Fas+ CD8 T cells in patients with confirmed metastases than in nonmetastatic. Next, we found that the percentage of FasL+ MTCs correlated with the frequency of Fas+ CD3 T cells in LNs aspirates and Fas+ CD8 T cells in PB. Finally, we found that patients with metastatic disease had a significantly higher FasL+/Fas+ MTCs ratio than patients with nonmetastatic disease. Both MTCs and CSCs express different immunomodulatory molecules on their surface. The frequency of FasL+ MTCs associates with altered distribution of Fas+ lymphocyte subpopulations in LNs and PB.

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Section: Discussionsupporting

confidence: 80%

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Raniszewska

Kwiecień

Sokołowski

et al. 2020

Cancers

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“…In many malignancies, existence of tumor cells in the tumor-draining lymph nodes (TDLN) is a key prognostic factor and sometimes predicates the course of treatment. Lymph nodes draining the primary tumor is a prerequisite for the initiation of an effective anti-tumor T cell immune response that constitutes the first line of defense against metastatic spread ( Murthy et al., 2019 ). Here, effective priming of cytotoxic CD8 + T cells (T c ) takes place upon tumor antigen recognition, presented by dendritic cells (DCs) and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Galunisertib Drives Treg Fragility and Promotes Dendritic Cell-Mediated Immunity against Experimental Lymphoma

et al. 2020

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Summary Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor-I activation, currently under clinical trial in a variety of cancers. We have tested the combined effects of galunisertib- and interleukin-15-activated dendritic cells in an aggressive and highly metastatic murine lymphoma. Based on the tumor-draining lymph node architecture, and its histology, the combination therapy results in better prognosis, including disappearance of the disease-exacerbating regulatory T cells. Our data suggest that galunisertib significantly enhances the success of immunotherapy with IL-15-activated dendritic cells by limiting the regulatory T cells generation with consequent downregulation of regulatory T cells in the tumor-draining lymph nodes and vascularized organ like spleen. This is also associated with consistent loss p-SMAD2 and downregulation of Neuropilin-1, leading to better prognosis and positive outcome. These results connect the role of combined therapy with the consequent elimination of disease-exacerbating T regulatory cells in a metastatic murine lymphoma.

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“…Murthy et al investigated the differences in the distributions of immune cells between drainage and non-drainage lymph nodes using samples from 20 NSCLC patients by flow cytometry. In their study, drainage lymph nodes showed a suppressive immunophenotype, having a lower proportion of effector CD4+ cells and a higher proportion of Tregs than the paired NRLNs (45). These findings suggest that because of the energy mediated by Tregs, the immune system against progression of carcinoma was attenuated, and such immunosuppressive microenvironment spread to lymph nodes around the tumor.…”

Section: Proportion Of Tregs In Tumor Normal Mucosa and Lymph Nodesmentioning

confidence: 90%

Distribution of Regulatory T-Cells and Other Phenotypes of T-Cells in Tumors and Regional Lymph Nodes of Colorectal Cancer Patients

Kazama

Otake

Satoyoshi

et al. 2020

In Vivo

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Tumor-draining lymph nodes demonstrate a suppressive immunophenotype in patients with non-small cell lung cancer assessed by endobronchial ultrasound-guided transbronchial needle aspiration: A pilot study

Cited by 11 publications

References 29 publications

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Galunisertib Drives Treg Fragility and Promotes Dendritic Cell-Mediated Immunity against Experimental Lymphoma

Distribution of Regulatory T-Cells and Other Phenotypes of T-Cells in Tumors and Regional Lymph Nodes of Colorectal Cancer Patients

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