Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma
Cleveland Clinic · Cleveland Clinic Lerner College of Medicine · +9 more institutions
Abstract
Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells.…
Citation impact
- FWCI
- 121.29
- Percentile
- 100%
- References
- 76
Authors
23- NLNatalie L. SilverCorresponding
Cleveland Clinic, Cleveland Clinic Lerner College of Medicine
- JDJin Dai
Cleveland Clinic Lerner College of Medicine
- TKTravis Kerr
University of Miami, Cleveland Clinic Lerner College of Medicine
- JAJessica Altemus
Cleveland Clinic Lerner College of Medicine
- RGRekha Garg
University of Florida
Topics & keywords
- Immunotherapy
- Tremelimumab
- Durvalumab
- Head and neck squamous-cell carcinoma
- Immune system
- Bacteria
- Blockade
- Immunity