Role of immune defenses in lung cancer therapy
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: 1. Cancer can result from failure of our immune system to reject tumors. 
 
 Cancer represents a normal and continuous biological process that is observed in all biological organisms, including plants. However, normal individual cancer cells are continuously eliminated by certain cells of our immune system. These cells are called T lymphocytes and represent a subset of our white blood cells. Normally, T cells are circulating in all compartments of our body and they are looking for the presence of invaders, such as bacteria and viruses, or for the presence of abnormal cells, such as cancer cells. This process, referred to as immune surveillance, insures a continuous protection against infection and cancer. However, for reasons that remain obscure to immunologists, the immune surveillance sometimes fails and cancer cells can proliferate and invade certain tissues or organs and form tumors; this phenomenon is known as immune escape. 
 
 
 
 
 
 2. The p53 gene-derived protein is an essential element of lung cancer
 
 The use of tobacco is associated with increased risk for lung cancer. Mutation in the p53 gene (and related changes in the production of its associated protein) is the most frequently reported gene alteration in human lung cancer; it is also associated with resistance to treatment such as radiotherapy and chemotherapy.
 
 
 
 
 
 Normally, proteins such as cancer-associated proteins are like flags presented at the surface of tumors alerting the immune system that something abnormal is happening. These proteins are presented to our immune system, not as a whole, but in the form of fragments. In our laboratory, we have performed a study which has shown that, during cancer, an immune response to p53 protein can be detected. Moreover, we have already identified to which portions (protein fragments) of p53 protein the immune response is directed. Finally, we have accumulated some evidence that indicates that the immune response to p53 is a dynamic process that changes during the course of cancer.
 
 
 
 
 
 This initial work gives us the unique opportunity to address the question of the immune escape of cancer cells. Our project is to use the model of p53 in lung cancer to: 
 
 
 
 
 
 1) analyze immune responses to p53 in cancer. We will determine why the immune system, although it recognizes 2 fragments of p53 on cancer cells, does not eliminate tumor-forming cells. To address this question, we will monitor the immune response to each of the fragments of p53 we previously identified at different stages of tumor formation. 
 
 
 
 
 
 2) design a cancer vaccine based on p53. We will immunize mice with each of the previously identified p53 fragments, either prior or during tumor formation. Then, we will test the effects of such treatments on the immune response to p53 molecule, the ability of immune cells to recognize cancer cells and prevent the formation or the progression of lung tumors.