Journal article
Immune checkpoint markers and anti‐CD20‐mediated NK cell activation
Journal of leukocyte biology, Vol.110(4), pp.723-733
10/2021
DOI: 10.1002/JLB.5A0620-365R
PMCID: PMC8184884
PMID: 33615552
Abstract
Anti-CD20 mAb is an effective therapy for most B-cell malignancies. Checkpoint blockade has been used to enhance T-cell-mediated antitumor response. Little is known about the biologic significance of immune checkpoints expressed by NK cells in anti-CD20-based therapy. To investigate the role of checkpoints in anti-CD20-mediated NK cell biology, Raji B-cell lymphoma cells, and PBMCs from normal donors were cocultured with rituximab (RTX), obinutuzumab (OBZ), or trastuzumab as a control mAb for between 20 h and 9 d. RTX and OBZ induced a dose-dependent NK cell up-regulation of T-cell immunoreceptor with Ig and ITIM domain (TIGIT) and T-cell immunoglobulin mucin-3 (TIM3), but not PD1, CTLA4, or LAG3. Resting CD56dim NK had higher TIGIT and TIM3 expression than resting CD56bright NK although TIGIT and TIM3 were up-regulated on both subsets. NK cells with the CD16 158VV single nucleotide polymorphism had greater TIM3 up-regulation than did NK from VF or FF donors. TIGIT+ and TIM3+ NK cells degranulated, produced cytokines, and expressed activation markers to a greater degree than did TIGIT– or TIM3– NK cells. Blockade of TIGIT, TIM3, or both had little impact on RTX-induced NK cell proliferation, degranulation, cytokine production, or activation. Taken together, TIGIT and TIM3 can serve as markers for anti-CD20-mediated NK cell activation, but may not serve well as targets for enhancing the anti-tumor activity of such therapy.
Details
- Title: Subtitle
- Immune checkpoint markers and anti‐CD20‐mediated NK cell activation
- Creators
- Zhaoming Wang - University of IowaGeorge J. Weiner - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.110(4), pp.723-733
- DOI
- 10.1002/JLB.5A0620-365R
- PMID
- 33615552
- PMCID
- PMC8184884
- NLM abbreviation
- J Leukoc Biol
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: P50 CA097274, P30 CA86862; DOI: 10.13039/100000002, name: National Institutes of Health, award: P50 CA097274, P30 CA86862
- Language
- English
- Date published
- 10/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984359576802771
Metrics
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