We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
NKG7 Enhances CD8+ T Cell Synapse Efficiency to Limit Inflammation.
- Authors
Lelliott, Emily J.; Ramsbottom, Kelly M.; Dowling, Mark R.; Shembrey, Carolyn; Noori, Tahereh; Kearney, Conor J.; Michie, Jessica; Parish, Ian A.; Jordan, Margaret A.; Baxter, Alan G.; Young, Neil D.; Brennan, Amelia J.; Oliaro, Jane
- Abstract
Cytotoxic lymphocytes are essential for anti-tumor immunity, and for effective responses to cancer immunotherapy. Natural killer cell granule protein 7 (NKG7) is expressed at high levels in cytotoxic lymphocytes infiltrating tumors from patients treated with immunotherapy, but until recently, the role of this protein in cytotoxic lymphocyte function was largely unknown. Unexpectedly, we found that highly CD8+ T cellimmunogenic murine colon carcinoma (MC38-OVA) tumors grew at an equal rate in Nkg7+/+ and Nkg7-/- littermate mice, suggesting NKG7 may not be necessary for effective CD8+ T cell anti-tumor activity. Mechanistically, we found that deletion of NKG7 reduces the ability of CD8+ T cells to degranulate and kill target cells in vitro. However, as a result of inefficient cytotoxic activity, NKG7 deficient T cells form a prolonged immune synapse with tumor cells, resulting in increased secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF). By deleting the TNF receptor, TNFR1, from MC38-OVA tumors, we demonstrate that this hyper-secretion of TNF compensates for reduced synapse-mediated cytotoxic activity against MC38-OVA tumors in vivo, via increased TNF-mediated tumor cell death. Taken together, our results demonstrate that NKG7 enhances CD8+ T cell immune synapse efficiency, which may serve as a mechanism to accelerate direct cytotoxicity and limit potentially harmful inflammatory responses.
- Subjects
T cells; TUMOR necrosis factors; CD8 antigen; KILLER cells; GRANULE cells
- Publication
Frontiers in Immunology, 2022, Vol 13, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.931630