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Supplemental Figures S1-5 from MICA-Expressing Monocytes Enhance Natural Killer Cell Fc Receptor-Mediated Antitumor Functions

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posted on 2023-04-03, 23:24 authored by Amanda R. Campbell, Megan C. Duggan, Lorena P. Suarez-Kelly, Neela Bhave, Kallan S. Opheim, Elizabeth L. McMichael, Prashant Trikha, Robin Parihar, Eric Luedke, Adrian Lewis, Bryant Yung, Robert Lee, David Raulet, Susheela Tridandapani, Veronika Groh, Lianbo Yu, Vedat Yildiz, John C. Byrd, Michael A. Caligiuri, William E. Carson

Supplemental Figure S1. Contribution of NK and T cells to IFN-gamma production. Supplemental Figure S2. MICA expression on monocytes. Supplemental Figure S3. NKG2D Ligand Expression on C1R and C1R-MICA Cell Lines. Supplemental Figure S4. Monocyte MICA expression does not correlate with NK cell IFN-gamma production. Supplemental Figure S5. NKG2D and MICA expression levels prior to and following co-culture.

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Susan G. Komen Breast Cancer Foundation

OSUCCC Pelotonia Graduate Fellowship

NIH

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ARTICLE ABSTRACT

Natural killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNγ, MIP-1α, and TNFα) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as IL12. We now demonstrate that this response is enhanced in the presence of autologous monocytes. Monocyte enhancement of NK cell activity was dependent on cell-to-cell contact as determined by a Transwell assay. It was hypothesized that NK cell effector functions against Ab-coated tumor cells were enhanced via binding of MICA on monocytes to NK cell NKG2D receptors. Strategies to block MICA–NKG2D interactions resulted in reductions in IFNγ production. Depletion of monocytes in vivo resulted in decreased IFNγ production by murine NK cells upon exposure to Ab-coated tumor cells. In mice receiving trastuzumab and IL12 therapy, monocyte depletion resulted in significantly greater tumor growth in comparison to mock-depleted controls (P < 0.05). These data suggest that NK cell–monocyte interactions enhance NK cell antitumor activity in the setting of monoclonal Ab therapy for cancer. Cancer Immunol Res; 5(9); 778–89. ©2017 AACR.

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    Cancer Immunology Research

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    Breast CancerImmunologyCytokinesImmunotherapyCellular immunotherapy

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