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1.
Oncoimmunology ; 13(1): 2346359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737794

RESUMEN

Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3+ T cells isolated from the peripheral blood (n = 20), malignant ascites (n = 16), and tumor tissue (n = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8+ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1high CD8+ T cell population was detected, which differed from PD-1lowCD8+ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8+ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (n = 14) and malignant ascites (n = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the "don't eat me" molecule CD24 on tumor cells. Additionally, ascites-derived CD24+EpCAM+ tumor cells showed a higher frequency of CD39+ or CD73+ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8+ T cells.


Asunto(s)
Apirasa , Linfocitos T CD8-positivos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Apirasa/metabolismo , Apirasa/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Persona de Mediana Edad , Ascitis/inmunología , Ascitis/patología , Ascitis/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Anciano , Receptor de Muerte Celular Programada 1/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/antagonistas & inhibidores , Factor 1 de Transcripción de Linfocitos T/metabolismo , Factor 1 de Transcripción de Linfocitos T/genética , Antígenos HLA-DR/metabolismo , Adulto , Agotamiento de Células T , Proteínas del Grupo de Alta Movilidad
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