T cell help in the tumor microenvironment enhances rituximab-mediated NK cell ADCC
Copyright © 2024 American Society of Hematology..
Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T cell help contributes to RTX-mediated NK cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T cell numbers in the lymphoma TME. In this model, NK cell viability, CD16 and CD25 expression dropped following RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In indolent lymphoma patients, fine needle aspirates were obtained prior to and approximately one week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pre-therapy TME, and an increase in NK cell CD16 and CD25 expression following RTX. We conclude that T cell help in the TME enhances RTX-mediated NK cell viability and ADCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Blood - (2024) vom: 08. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arora, Jyoti [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 24.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1182/blood.2023023370 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36947094X |
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| 520 | |a Copyright © 2024 American Society of Hematology. | ||
| 520 | |a Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T cell help contributes to RTX-mediated NK cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T cell numbers in the lymphoma TME. In this model, NK cell viability, CD16 and CD25 expression dropped following RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In indolent lymphoma patients, fine needle aspirates were obtained prior to and approximately one week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pre-therapy TME, and an increase in NK cell CD16 and CD25 expression following RTX. We conclude that T cell help in the TME enhances RTX-mediated NK cell viability and ADCC | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Yin, Chaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Brian J |e verfasserin |4 aut | |
| 700 | 1 | |a Lemke-Miltner, Caitlin Danielle |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Farooq, Umar |e verfasserin |4 aut | |
| 700 | 1 | |a Weiner, George J |e verfasserin |4 aut | |
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