Journal article
T cell help in the tumor microenvironment enhances rituximab-mediated NK cell ADCC
Blood, Vol.143(18), pp.1816-1824
05/02/2024
DOI: 10.1182/blood.2023023370
PMCID: PMC11076912
PMID: 38457360
Abstract
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.
Details
- Title: Subtitle
- T cell help in the tumor microenvironment enhances rituximab-mediated NK cell ADCC
- Creators
- Jyoti Arora - University of IowaSabarish Ram Ayyappan - University of IowaChaobo Yin - University of IowaBrian J Smith - University of Iowa, Iowa City, Iowa, United StatesCaitlin Danielle Lemke-Miltner - University of IowaZhaoming Wang - University of IowaUmar Farooq - University of Iowa Hospitals and Clinics, Iowa City, Iowa, United StatesGeorge J Weiner - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.143(18), pp.1816-1824
- DOI
- 10.1182/blood.2023023370
- PMID
- 38457360
- PMCID
- PMC11076912
- NLM abbreviation
- Blood
- eISSN
- 1528-0020
- Language
- English
- Electronic publication date
- 03/08/2024
- Date published
- 05/02/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984568047902771
Metrics
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