Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.

Miguel-García, A; Matutes, E.; Tarín, Fabián; J, García-Talavera; Miguel-Sosa, A; Carbonell, F; D, Catovsky

doi:10.1136/jcp.48.9.835

Cited by 19 publications

(3 citation statements)

References 21 publications

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“…Conventional natural killer cell proliferation was measured after T. gondii infection by intracellular staining for nuclear Ki67, a marker of cell cycle progression and a surrogate marker of cellular proliferation ( 40 , 41 ). cNK cells did not appear to undergo proliferation at 5 days post infection in the PEC or spleen with any of the parasite strains tested (Figures 7 C,D).…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Conventional Natural Killer Cell Responses to Acute Infection with Toxoplasma gondii Strains of Different Virulence

2016

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Conventional natural killer (cNK) cells, members of group 1 innate lymphoid cells, are a diverse cell subpopulation based on surface receptor expression, maturation, and functional potential. cNK cells are critical for early immunity to Toxoplasma gondii via IFNγ production. Acute cNK cell responses to infection with different strains of T. gondii have not yet been characterized in detail. Here, we comprehensively performed this analysis with Type I virulent RH, Type II avirulent ME49, and fully attenuated Type I cps1-1 strains. In response to these three parasite strains, murine cNK cells produce IFNγ and become cytotoxic and polyfunctional (IFNγ+CD107a+) at the site of infection. In contrast to virulent RH and avirulent ME49 T. gondii strains, attenuated cps1-1 induced only local cNK cell responses. Infections with RH and ME49 parasites significantly decreased cNK cell frequency and numbers in spleen 5 days post infection compared with cps1-1 parasites. cNK cell subsets expressing activating receptors Ly49H, Ly49D, and NKG2D and inhibitory receptors Ly49I and CD94/NKG2A were similar when compared between the strains and at 5 days post infection. cNK cells were not proliferating (Ki67−) 5 days post infection with any of the strains. cNK cell maturation as measured by CD27, CD11b, and KLRG1 was affected after infection with different parasite strains. RH and ME49 infection significantly reduced mature cNK cell frequency and increased immature cNK cell populations compared with cps1-1 infection. Interestingly, KLRG1 was highly expressed on immature cNK cells after RH infection. After RH and ME49 infections, CD69+ cNK cells in spleen were present at higher frequency than after cps1-1 infection, which may correlate with loss of the mature cNK cell population. Cytokine multiplex analysis indicated cNK cell responses correlated with peritoneal exudate cell, spleen, and serum proinflammatory cytokine levels, including IL-12. qPCR analysis of parasite-specific B1 gene revealed that parasite burdens may affect cNK cell responses. This study demonstrates infection with RH and ME49 parasites impacts cNK cell maturation during acute T. gondii infection. Different cNK cell responses could impact early immunity and susceptibility to these strains.

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Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Conventional Natural Killer Cell Responses to Acute Infection with Toxoplasma gondii Strains of Different Virulence

2016

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“…Ki‐67 has been shown to be exclusively expressed in the cells that have entered into G1, S, G2 and M phase of the cell cycle and is not expressed in resting cells [14–16]. The monoclonal antibody (MoAb) recognizing Ki‐67 has been widely used to assess the proliferation rate in a variety of malignant tumors [15, 17–19] and few studies have analyzed the expression of Ki‐67 in non‐neoplastic conditions [18, 20]. A two‐colour immunoenzymatic staining method with microwave heat treatment to increase the accessibility of the nuclear antigens was designed to identify the surface phenotype and nuclear expression of Ki‐67 simultaneously as described previously [21, 22].…”

Section: Introductionmentioning

confidence: 99%

Activation of T Cells in the Blood of Patients with Acute Malaria: Proliferative Activity as Indicated by Ki‐67 Expression

et al. 2001

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The expression of the proliferation-associated nuclear antigen Ki-67 in peripheral blood mononuclear cells was studied in 30 patients with acute malarial illness and 11 healthy controls from Addis Ababa or Nazareth in Ethiopia. Seventeen patients had Plasmodium falciparum infections and 13 had Plasmodium vivax. Twocolour immunoenzymatic staining was developed in order to simultaneously detect the expression of the nuclear antigen Ki-67 and determine the surface phenotype of the cell. The median percentage of proliferating, Ki-67 positive lymphocytes was significantly higher in patients with acute P. falciparum (11.8%) and P. vivax (15.6%) illnesses compared to the controls (4.3%). The majority of Ki-67 positive cells were T cells (CD3 1 ) while the relative increase of Ki-67 expressing cells was similar for both the CD4 1 and CD8 1 T-cell subsets. Our data show an increased number of activated cells driven to proliferation in the peripheral blood of patients during acute malaria illness.

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“…MKI67 , AURKA , TOP2A and UBE2C were highly expressed in Ki67 + T cells, indicating an active proliferation status and potential contribution to the occurrence, development, and metastasis of UBC. Ki67 + T cell subsets were previously identified in colorectal cancer 36 and multiple myeloma 37 . Moreover, the percentage of Ki67 + lymphocytes was significantly higher in patients with multiple myeloma and monoclonal gammopathy compared with the normal controls, which was associated with disease stage.…”

Section: Discussionmentioning

confidence: 98%

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis

Guo

Wang

Bai

et al. 2023

Sci Rep

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Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

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Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.

Cited by 19 publications

References 21 publications

Comparative Analysis of Conventional Natural Killer Cell Responses to Acute Infection with Toxoplasma gondii Strains of Different Virulence

Comparative Analysis of Conventional Natural Killer Cell Responses to Acute Infection with Toxoplasma gondii Strains of Different Virulence

Activation of T Cells in the Blood of Patients with Acute Malaria: Proliferative Activity as Indicated by Ki‐67 Expression

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis

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