Biological Significance and Predictive Value of Analyzing the PD-1 Axis and Tumor Infiltrating Lymphocytes in Lung Cancer
Abstract
After decades of generally disappointing results with immunotherapy of cancer, recent efforts to pharmacologically block the so-called "immune checkpoints" have shown prominent clinical benefit in different cancer types. In particular, blockade of the biological pathway conformed by the checkpoints PD-1 and PD-L1 induce durable responses in nearly 20% of patients with advanced lung cancer. Unfortunately, there are currently no mechanisms or clinical tests that can unequivocally identify patients with the highest potential of benefit from these therapies. Therefore, treatments are given to all patients, leading to frequent overtreatment, futile toxicity, and excessive costs. It has been suggested that the presence of the protein PD-L1 or of inflammatory cells in the tumor is associated with clinical benefit, but traditional methods to detect markers in tumor samples have limited output and are not reproducible. In this project, we propose to use novel technologies to interrogate the tumor tissues in a more exact manner. We will carefully study the PD-1 checkpoint pathway and the inflammation of lung cancers to understand their biology and develop a test to accurately predict response to immunotherapy. The results from this project will also contribute to understand the mechanisms used by tumors to escape immunity, disseminate, and become a life-threatening disease. The Principal Investigator (PI) of this proposal is a surgical pathologist that has committed to a research career in lung cancer and was recently recruited as an Assistant Professor at Yale. His career goals are to become a top independent lung cancer researcher and focus on subjects that will have direct impact in patient care. During his initial steps, he will be mentored by leaders in the field of lung immuno-oncology and will be nurtured by a premier thoracic oncology program. This Career Development Award will be a unique opportunity to support the PI to perform outstanding translational lung cancer research and use his skills to advance the field. In addition, having this award will position him well for independence. The results from the proposed project could produce a new test to select lung cancer patients for novel immunotherapies. In addition, this test could be rapidly introduced to the clinic and directly benefit patients with advanced lung cancer. Understanding the immune checkpoint pathway and the tumor inflammation could also be used to devise new treatment options. Finally, this proposal has the potential to favorably impact the management of lung cancer, a disease frequently affecting military personnel and Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610160
Entities
People
- Kurt Schalper
Organizations
- United States Army
- Yale University