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Translational Tumor Immunology Program
Clint T. Allen, M.D., Otolaryngology Surgeon-Scientist
The Translational Tumor Immunology Program focuses on immunologic aspects of cancer development and progression, with a focus on head and neck squamous cell carcinoma, the most common form of head and neck cancer.
To study head and neck cancer, we use syngeneic models of oral cavity cancer that allows the study of both cancer cells themselves and how they interact with immune cells in tumors. The goals of our lab are 1) to understand how standard-of-care and investigational anti-cancer treatments alter cancer cells to make them more or less susceptible to immune cell killing, and 2) to understand how these same drugs alter the ability of immunosuppressive cells within the tumor microenvironment to block effective anti-tumor immunity. Ultimately, this will lead to a better understanding of how to combine drugs that both kill tumor cells and enhance the body’s natural anti-tumor immune response. Using this information, several clinical trials aimed at improving response to therapy and survival in patients with head and neck cancer are being developed.
Our work also aims to translate key knowledge learned from our investigation into anti-tumor immunity to other diseases in otolaryngology, including inflammatory and infectious disorders.
- Davis RJ, Moore EC, Clavijo PE, Friedman J, Cash HA, Chen Z, Silvin C, Van Waes C, Allen CT. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid derived suppressor cells with a selective inhibitor of PI3Kδ/γ. Cancer Res. 2017 Mar 31.
- Davis RJ, Silvin C, Allen CT. Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays. J Immunol Methods. 2016 Nov 14.
- Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, Allen C. Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway blockade. Cancer Immunol Res. 2016 Nov 7.
- Davis R, Van Waes C, Allen CT. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol. 2016 May 20. pii: S1368-8375(16)30045-8.
- Moore EC, Cash HA, Caruso AM, Uppaluri R, Hodge JW, Van Waes C, Allen CT. Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancer. Cancer Immunol Res. 2016 Apr 13. pii: canimm.0252.2015.
- Shah S, Caruso A, Cash H, VanWaes, C, Allen C. Pools of programmed death ligand within the oral cavity tumor microenvironment: variable alteration by targeted therapies. Head and Neck. 2016 Apr 9. doi: 10.1002/hed.24269.
- Allen CT, Clavijo PE, Van Waes C, Chen Z. Anti-tumor immunity in head and neck cancer: Understanding the evidence, how tumors escape and immunotherapeutic approaches. Cancers. 2015 Dec 9;7(4):2397-414.
- Cash H, Shah S, Caruso A, VanWaes C, Allen C. mTOR and MEK1/2 inhibition modulate tumorigenesis and the immune microenvironment in syngeneic models of oral cavity cancer. Oncotarget. 2015 Nov 3;6(34):36400-17.
- Allen CT, Conley B, Sunwoo JB, Van Waes C. CCR 20th Anniversary Commentary: Preclinical Study of Proteasome Inhibitor Bortezomib in Head and Neck Cancer. Clin Cancer Res. 2015 Mar 1;21(5):942-3.
- Nottingham LK, Yan CH, Yang X, Si H, Coupar J, Bian Y, Cheng TF, Allen C, Arun P, Gius D, Dang L, Van Waes C, Chen Z. Aberrant IKKα and IKKβ cooperatively activate NF-κB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer. Oncogene. 2014 Feb 27;33(9):1135-47.
- Allen C, Law J, Dunn, G, Uppaluri R. Emerging insights into head and neck cancer metastasis. Head Neck. 2013 Nov;35(11):1669-78.
- Allen C, Judd N, Winkler A, Uppaluri R. Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer. Otolaryngol Head Neck Surg. 2012 Sep;147(3):493-500.
- Allen C, Judd N, Bui J, Uppaluri R. The clinical implications of antitumor immunity in head and neck cancer. Laryngoscope. 2012 Jan;122(1):144-57.
- Lu H, Yang X, Duggal P, Allen CT, Yan B, Cohen J, Nottingham L, Romano RA, Sinha S, King KE, Weinberg WC, Chen Z, Van Waes C. TNF-α promotes c-REL/ΔNp63α interaction and TAp73 dissociation from key genes that mediate growth arrest and apoptosis in head and neck cancer. Cancer Res. 2011 Nov 1;71(21):6867-77.
- Yang X, Lu H, Yan B, Romano RA, Bian Y, Friedman J, Duggal P, Allen C, Chuang R, Ehsanian R, Si H, Sinha S, Van Waes C, Chen Z. ΔNp63 versatilely regulates a Broad NF-κB gene program and promotes squamous epithelial proliferation, migration, and inflammation. Cancer Res. 2011 May 15;71(10):3688-3700.
- Allen CT, Lewis JS Jr, El-Mofty SK, Haughey BH, Nussenbaum B. Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope. 2010 Sep;120(9):1756-72.
- Van Waes C, Allen CT, Citrin D, Gius D, Colevas AD, Harold NA, Rudy S, Nottingham L, Muir C, Chen Z, Singh AK, Dancey J, Morris JC. Molecular and clinical responses in a pilot study of gefitinib with paclitaxel and radiation in locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):447-54.