Tumor-Associated Neutrophils in Human Lung Cancer
Abstract
Scientific Objective and Rationale: Lung cancer is the most common cause of cancer death among Veterans in the United States. One explanation for the high frequency of lung cancer in Veterans is that up to 40% of military personnel and Veterans currently smoke, and 77% of all Veterans have smoked during their lifetime. Using a patients own immune system to identify and attack a lung cancer is an attractive proposition, and it has been a subject of tumor immunotherapy for two decades. Over the last several years, we have learned that previous attempts were unsuccessful due to the failure to address the influence of the tumor microenvironment. A better understanding of the interaction between cancer cells and the lung microenvironment will allow tumor immunologists to develop new methods to improve anti-tumor immune responses. Specifically, tumor-recruited myeloid cells represent a significant portion of inflammatory cells in the tumor microenvironment and influence nearly all steps of tumor progression. Tumor-associated neutrophils (TANs) are the predominant cell type of these cells. However, virtually nothing is known about these cells even though they can account for as much as 60% of the tumor. The research objective of this proposal is to determine the specific roles of distinct subsets of TANs in human lung cancers and to develop novel approaches to boost anti-tumor immunity. Our proposed study will address two Lung Cancer Research Program Areas of Emphasis: (i) understanding the molecular mechanisms of progression to clinically significant lung cancer and (ii) identification of innovative strategies for prevention and treatment of early and/or localized lung cancer. Principal Investigator s Career Goals in Lung Cancer Research: My career goal is to become a funded independent investigator and provide meaningful input into the field of lung cancer therapy. I was hired by the Thoracic Oncology Research Laboratory as an Assistant Professor, thus my entire career focus is on lung cancer. My specific research goal in lung cancer is to develop new ways to enhance a patients own immune response to tumors by disrupting tumor-induced tolerance/suppression. The completion of this proposed study will generate new knowledge about human TANs and exert a sustained influence on the field. This study will take advantage of my skills and expertise. My long-term interest and expertise in tumor-associated myeloid cells are well documented by my publications. Successful completion of this work will set the stage for a larger grant proposal to enhance current T cell therapies and amplify anti-tumor TAN responses. This work is a first-of-its kind and will surely impact the whole field of tumor immunotherapy and dramatically advance my career as a researcher in the field of human lung tumor microenvironment. Applicability of the Research: We will study the tumors of a large cohort of Veterans and their family members that were diagnosed with lung cancer in the Philadelphia Veterans Affairs (VA) Medical Center. We intend to enroll 125 patients who have non-small cell lung cancer (NSCLC) and good performance status and are suitable candidates for surgery. This proposal and all the informed consent forms have been reviewed and approved by the Human Studies Committees at the Philadelphia VA Medical Center, Institutional Review Board. No research will be performed on humans directly. The involvement of human subjects is limited to the use of tumor tissue, surrounding lung, lymph nodes, and blood obtained at the time of surgery on these Veterans. Our proposed study will develop a better understanding of the role of intratumoral inflammatory cells in tumor progression and open new therapeutic options in the future design of active immunotherapy to enhance current lung cancer treatments. First, we will determine whether TAN subsets actively suppress or support T cell response in early stage lung cancer. Our proposed
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510717
Entities
People
- Evgeniy B Eruslanov
Organizations
- United States Army
- University of Pennsylvania