Brendon Stiles, MD, is Professor and Chief, Thoracic Surgery and Surgical Oncology, Department of Cardiothoracic & Vascular Surgery at Montefiore-Einstein.  Dr. Stiles is also the Associate Director for Surgical Services in the Montefiore-Einstein Cancer Center. Dr. Stiles’ clinical focus is on the treatment of lung and esophageal cancer and on neoadjuvant immunotherapy. Taking a patient-first philosophy, Dr. Stiles provides world-class personalized care, using minimally invasive, organ-sparing techniques and targeting surgical therapy to the specific needs of the patient and his or her individual tumor.

Dr. Stiles is also heavily involved with translational and basic research.  Translationally, Dr. Stiles is interested in neoadjuvant immunotherapy and in predicting and augmenting response to immunotherapy.   In the laboratory, he has been funded by the AATS, TSF, the Lung Cancer Research Foundation, the DOD CDMRP Lung Cancer Research Program, and the Mark Foundation. 

Dr. Stiles' laboratory currently investigates the protein ART1, an extracellular mono-ADP-ribosyltransferase.  Recently, Dr. Stiles and his team discovered that ART1 may play an important role in one mechanism of resistance in lung cancers. ART1 mono-ADP-ribosylates the P2X7 receptor (P2X7R) on immune cells, which ultimately causes NAD-induced cell death (NICD) in T cells, macrophages, and dendritic cells. They found ART1 to be highly expressed in multiple human non-small cell lung cancer cell lines and in the majority of human lung adenocarcinomas they sampled.  ART1 expression allows cancers to blunt the immune response against them. Indeed, they found that inhibiting ART1 with a therapeutic monoclonal antibody in mouse models of lung cancer caused a dramatic reduction of tumor burden and an enrichment of immune cells in the tumor.

Current efforts are underway to better understand regulation of ART1 expression, to identify more targets of extracellular mono-ADP-ribosylation, and to refine pre-clincal models to test their therapeutic antibody targeting ART1.

Wennerberg, Erik et al, Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.  Science Translational Medicine. 2022 Mar 16;14(636):eabe8195.  https://www.science.org/stoken/author-tokens/ST-384/full

Altorki, Nasser K., et al. "The lung microenvironment: an important regulator of tumour growth and metastasis." Nature Reviews Cancer 19.1 (2019): 9-31.

Yao, Zhan, et al. "TGF-β IL-6 axis mediates selective and adaptive mechanisms of resistance to molecular targeted therapy in lung cancer." Proceedings of the National Academy of Sciences 107.35 (2010): 15535-15540.

Gao, Dingcheng, et al. "Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition." Cancer research 72.6 (2012): 1384-1394.

Altorki, Nasser K., et al. "Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: A single-centre, randomised phase 2 trial." The Lancet Oncology 22.6 (2021): 824-835.

Wennerberg, Erik, et al. "Expression of ART1, an extracellular mono ADP-ribosylase, promotes lung cancer growth and dissemination by limiting tumor infiltration of P2X7R+ CD8+ T cells and CD103+ dendritic cells." JOURNAL FOR IMMUNOTHERAPY OF CANCER. Vol. 7. CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND: BMC, 2019.

Chen, Chuang, et al. "ART1, an extracellular ADP-ribosyltransferase, is over-expressed in non-small cell lung cancer and facilitates cancer cell survival by immune-mediated mechanisms." Journal of Thoracic Oncology 11.2 (2016): S44.

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