PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection

Macfarlane, Alexander W.; Jillab, Mowafaq; Plimack, Elizabeth R.; Hudes, Gary R.; Uzzo, Robert G.; Litwin, Samuel; Dulaimi, Essel; Al‐Saleem, Tahseen; Campbell, Kerry S.

doi:10.1158/2326-6066.cir-13-0133

Cited by 146 publications

(127 citation statements)

References 50 publications

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“…In these studies the expression of PD-1 was detected in PB NK cells derived from patients 37,38,59,60 but not from HDs. In addition, the level of expression reported was very low, thus rendering it difficult to discriminate between PD-1 1 and PD-1 2 cells and to identify a distinct subset of PD-1 1 cells.…”

Section: Discussionmentioning

confidence: 79%

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Pesce

Greppi

Tabellini

et al. 2017

Journal of Allergy and Clinical Immunology

382

386

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Background: Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells. Objective: We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features. Methods: We performed multiparametric cytofluorimetric analysis of PD-1 1 NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays. Results: We provide unequivocal evidence that PD-1 is highly expressed (PD-1 bright ) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56 dim but not CD56 bright NK cells and is confined to fully mature NK cells characterized by the NKG2A 2 KIR 1 CD57 1 phenotype. Proportions of PD-1 bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their

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Section: Discussionmentioning

confidence: 79%

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Pesce

Greppi

Tabellini

et al. 2017

Journal of Allergy and Clinical Immunology

382

386

View full text Add to dashboard Cite

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“…Signaling downstream of PD-1 is mediated by the presence of an immunoreceptor tyrosine-based switch motif (ITSM) and an immunoreceptor tyrosine-based inhibitory motif (ITIM) that recruit anti-SRC homology phosphatase (SHP)-1 and SHP-2 protein tyrosine phosphatases to modulate inhibitory signaling [Nirschl et al 2013;MacFarlane et al 2014]. PD-1 is inducibly expressed on CD4+ and CD8+ T cells, NK cells, B cells and monocytes within 24 h from their immunological activation [Keir et al 2008].…”

Section: Introductionmentioning

confidence: 99%

Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Mennitto

Grassi

Ratta

et al. 2016

Therapeutic Advances in Urology

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Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future.

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“…The migration, invasion, conglutination and growth analyses of cancer cells are the most commonly used methods to judge cytoactivity. These methods can reflect the fact that the tumor leaves the primary tumor extracellular matrix (11)(12)(13)(14)(15). In the present study, it was found that the reproduction rate of the tumor cells was relatively low in the early passage.…”

Section: A B C D E F Discussionmentioning

confidence: 99%

“…At present, a number of studies have confirmed that PD-1 is a synergistic inhibitory receptor, which can regulate T cell proliferation (12,22). The antigen-stimulated high expression of PD-1 on the CD8 + T-cell surface is associated with T-cell depletion.…”

Section: A B C D E F Discussionmentioning

confidence: 99%

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

Zhao

Dai

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to investigate the effect of programmed cell death 1 (PD-1) on osteosarcoma (OD) stem cells and T cells, and to determine their correlation. OS stem cells were sorted and identified from OS MG63 cells. Flow cytometry was used to detect the PD-1 expression of the OS tumor stem cell membrane surface. The expression of PD-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). MTT was used to detect the effect of PD-1 signals on T-cell proliferation. The results indicated that the cancer cells (cultured in DMEM medium containing 10% fetal bovine serum) exhibited clear proliferation within 1 week of cell culture, which showed their strong proliferation and aggressive ability. The formation of tumor cell spheres was dependent on the support of serum nutrition. The proliferation of MG63 cells in the serum culture medium was significantly higher than the number of OS cell spheres in serum-free suspension culture (P<0.05). Pluripotent stem cells in cancer cell spheres exhibited significantly higher cluster of differentiation 133 expression compared with the MG63 cells. The PD-1 expression levels of the cancer cell spheres was significantly increased compared with the MG63 cells, which is consistent with the results of the RT-PCR. In conclusion, the MG63 cell line possesses the features of OS stem cells. The MG63 cell line can express the certain cancer-associated cell markers. The expression of PD-1 in spheres was also increased significantly compared to the MG63 cells, which can reduce the immune function of patients and may be closely associated with the occurrence and development of tumors.

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PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection

Cited by 146 publications

References 50 publications

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization

Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

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