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Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction

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Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction. / Marius, Witt; Leticia, Oliveira-Ferrer; Friedrich, Koch-Nolte; Stephan, Menzel; Louisa, Hell; Tabea, Sturmheit; Elisa, Seubert; Pauline, Weimer; Yi, Ding; Qi, Minyue; Barbara, Schmalfeldt; Carsten, Bokemeyer; Walter, Fiedler; Jasmin, Wellbrock; Franziska, Brauneck.

In: ONCOIMMUNOLOGY, Vol. 13, No. 1, 2024, p. 2346359.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Marius, W, Leticia, O-F, Friedrich, K-N, Stephan, M, Louisa, H, Tabea, S, Elisa, S, Pauline, W, Yi, D, Qi, M, Barbara, S, Carsten, B, Walter, F, Jasmin, W & Franziska, B 2024, 'Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction', ONCOIMMUNOLOGY, vol. 13, no. 1, pp. 2346359. https://doi.org/10.1080/2162402X.2024.2346359

APA

Marius, W., Leticia, O-F., Friedrich, K-N., Stephan, M., Louisa, H., Tabea, S., Elisa, S., Pauline, W., Yi, D., Qi, M., Barbara, S., Carsten, B., Walter, F., Jasmin, W., & Franziska, B. (2024). Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction. ONCOIMMUNOLOGY, 13(1), 2346359. https://doi.org/10.1080/2162402X.2024.2346359

Vancouver

Marius W, Leticia O-F, Friedrich K-N, Stephan M, Louisa H, Tabea S et al. Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction. ONCOIMMUNOLOGY. 2024;13(1):2346359. https://doi.org/10.1080/2162402X.2024.2346359

Bibtex

@article{b62badff2ed64532a2529998d3f982ad,
title = "Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction",
abstract = "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.",
keywords = "Humans, Female, Ovarian Neoplasms/immunology, Apyrase/metabolism, CD8-Positive T-Lymphocytes/immunology, Middle Aged, Ascites/immunology, Antigens, CD/metabolism, Aged, Programmed Cell Death 1 Receptor/metabolism, Receptors, Immunologic/metabolism, T Cell Transcription Factor 1/metabolism, HLA-DR Antigens/metabolism, Adult, T-Cell Exhaustion, High Mobility Group Proteins",
author = "Witt Marius and Oliveira-Ferrer Leticia and Koch-Nolte Friedrich and Menzel Stephan and Hell Louisa and Sturmheit Tabea and Seubert Elisa and Weimer Pauline and Ding Yi and Minyue Qi and Schmalfeldt Barbara and Bokemeyer Carsten and Fiedler Walter and Wellbrock Jasmin and Brauneck Franziska",
note = "{\textcopyright} 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2024",
doi = "10.1080/2162402X.2024.2346359",
language = "English",
volume = "13",
pages = "2346359",
journal = "ONCOIMMUNOLOGY",
issn = "2162-402X",
publisher = "Taylor & Francis",
number = "1",

}

RIS

TY - JOUR

T1 - Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction

AU - Marius, Witt

AU - Leticia, Oliveira-Ferrer

AU - Friedrich, Koch-Nolte

AU - Stephan, Menzel

AU - Louisa, Hell

AU - Tabea, Sturmheit

AU - Elisa, Seubert

AU - Pauline, Weimer

AU - Yi, Ding

AU - Qi, Minyue

AU - Barbara, Schmalfeldt

AU - Carsten, Bokemeyer

AU - Walter, Fiedler

AU - Jasmin, Wellbrock

AU - Franziska, Brauneck

N1 - © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Humans

KW - Female

KW - Ovarian Neoplasms/immunology

KW - Apyrase/metabolism

KW - CD8-Positive T-Lymphocytes/immunology

KW - Middle Aged

KW - Ascites/immunology

KW - Antigens, CD/metabolism

KW - Aged

KW - Programmed Cell Death 1 Receptor/metabolism

KW - Receptors, Immunologic/metabolism

KW - T Cell Transcription Factor 1/metabolism

KW - HLA-DR Antigens/metabolism

KW - Adult

KW - T-Cell Exhaustion

KW - High Mobility Group Proteins

U2 - 10.1080/2162402X.2024.2346359

DO - 10.1080/2162402X.2024.2346359

M3 - SCORING: Journal article

C2 - 38737794

VL - 13

SP - 2346359

JO - ONCOIMMUNOLOGY

JF - ONCOIMMUNOLOGY

SN - 2162-402X

IS - 1

ER -