journal contribution
posted on 2023-04-03, 23:07 authored by Ellen Moore, Paul E. Clavijo, Ruth Davis, Harrison Cash, Carter Van Waes, Young Kim, Clint Allen Details additional immune correlative changes in treated MOC1 tumors, immune correlative changes in treated MOC2 tumors, and provides validation of the in vivo CTL assay.
Funding
NIH, NIDCD
NIH Medical Research Scholars Program
Pfizer Inc
The Doris Duke Charitable Foundation
The Newport Foundation
The American Association for Dental Research
The Howard Hughes Medical Institute
American Academy of Otolaryngology/American Head and Neck Society Duane Sewell Young Investigators Award
History
ARTICLE ABSTRACT
Patients with head and neck squamous cell carcinoma harbor T cell–inflamed and non–T cell–inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell–inflamed (MOC1), but not non–T cell–inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP. Rejection or durable tumor control of MOC1 tumors was dependent upon a functional STING receptor and CD8 T lymphocytes. STING activation resulted in increased tumor microenvironment type 1 and type 2 IFN and greater expression of PD-1 pathway components in vivo. Established MOC1 tumors were rejected and distant tumors abscopally controlled, after adaptive immune resistance had been reversed by the addition of PD-L1 mAb. These findings suggest that PD-1 pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity. Cancer Immunol Res; 4(12); 1061–71. ©2016 AACR.
