PD1 blockade enhances K+channel activity, Ca2+signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer
Abstract
Immunotherapy has emerged as a promising treatment modality for head and neck squamous cell carcinoma (HNSCC). Pembrolizumab, an anti-programmed death 1 antibody, is an immunotherapy agent currently approved for metastatic HNSCC and curative intent clinical trials. Although clinical responses to pembrolizumab are promising, many patients fail to respond. However, it is well known that T cell cytotoxicity and chemotaxis are critically important in the elimination of HNSCC tumors. These functions depend on ion channel activity and downstream Ca2+fluxing abilities, which are defective in patients with HNSCC. The purpose of this study was to elucidate the effects of pembrolizumab on potassium (K+) channel (KCa3.1 and Kv1.3) activity, Ca2+fluxes, and chemotaxis in the cytotoxic T cells of patients with HNSCC and to determine their correlation with treatment response.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2020
- Source ID
- 10.1136/jitc-2020-000844
Entities
People
- Ameet A. Chimote
- Benjamin H. Hinrichs
- David Hildeman
- Edith M. Janssen
- Hannah S Newton
- Laura Conforti
- Maria A Lehn
- Roman Jandarov
- Sarah M Palackdharry
- Trisha M Wise-Draper
- Vaibhavkumar S Gawali
Organizations
- Merck & Co.
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense