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Mechanisms of Immunosurveillance for Lung Cancer-the Role of CD8+ T Cells in Tumor Tolerance Induction

肺癌免疫监视机制——CD8 T细胞在肿瘤耐受诱导中的作用

基本信息

批准号：
10255913
负责人：
ALEXANDER S. KRUPNICK
金额：
--
依托单位：
BALTIMORE VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2025-09-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10255913
关键词：
Adjuvant Affect Animal Model Award Belief Blood CD8-Positive T-Lymphocytes CD8B1 gene Cancer Biology Cancer Patient Carcinogens Cause of Death Cell Line Cells Clinical Clinical Data Consumption Data Development Disease Down-Regulation Environment Failure Gastrointestinal tract structure Gene Silencing General Population Genetic Transcription Graft Rejection Growth Human Immune Tolerance Immune response Immune system Immunologic Surveillance Immunologics Immunotherapy Interferons Laboratories Lewis lung carcinoma cell Lung Lung Transplantation Lymphocyte Lymphoid Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Mediating Mediator of activation protein Memory Military Personnel Modeling Mucous Membrane Mus Natural Killer Cells Non-Small-Cell Lung Carcinoma Organ Organ Transplantation Patients Peptides Pharmaceutical Preparations Pharmacologic Substance Phenotype Play Population Protocols documentation Role Series Skin Solid Neoplasm T cell differentiation T memory cell T-Lymphocyte TNF gene Techniques Testing Tissues Transplantation United States Vaccination Veterans Western World Work amino acid metabolism animal data base cancer immunotherapy clinical application cytokine cytotoxic cytotoxicity high risk immunoregulation immunotherapy clinical trials immunotherapy trials improved melanoma military veteran mouse model novel novel therapeutic intervention overexpression pre-clinical programmed cell death ligand 1 rational design response success synaptogenesis tumor tumor growth tumor microenvironment

项目摘要

Lung cancer remains the major cancer-related cause of death in the Western World and intense efforts are directed toward the development of immunotherapy for the treatment of this disease. While immunotherapy targeting cytotoxic T (CD8+ T) lymphocytes has been successful in several malignancies, such as melanoma and prostate cancer, it has demonstrated only limited success in lung cancer. Based on our laboratory’s work in lung transplantation, where we have demonstrated a tolerogenic role for alloreactive CD8+ T cells, we have now generated preclinical animal data which demonstrates that, unlike the case for other malignancies, the presence of conventional CD8+ T cells can accelerate the growth of both transplantable as well as carcinogen-induced lung cancer in a murine model. In this Merit Award application we propose a series of coordinated but non-overlapping specific aims to delineate the tolerogenic role of CD8+ T cells in lung cancer, identify mechanisms responsible for CD8+ T cell-mediated downregulation of the immune response, as well as define the interaction of CD8+ T cells with natural killer cells. This proposal will extend our understanding of lung cancer-specific immunoregulation and generate novel preclinical data that can be utilized for rational design of lung cancer- specific novel therapeutic approaches for Veterans and the general population.

肺癌仍然是西方世界主要的癌症相关死亡原因