Breaking the Immune Tolerance Induced by Apoptotic Cancer Cells
报告题目: Breaking the Immune Tolerance Induced by Apoptotic Cancer Cells
报告人：Yi Ban Ph.D
Department of Microbiology and Immunology
Weill Cornell Medical College, New York
NY
时间：2014年 6 月 6 日（周五）下午4: 15 – 5: 15
地点：数学楼二楼学术报告厅
Large-scale cell death occurs in cancer treatment by conventional irradiation and chemotherapy. Clearance of the dying or dead cells in the body is mainly carried out by professional “scavengers” called phagocytes. This is an evolutionarily well conserved way to “cleansing” the bodily system of cellular debris and wastes, and to prevent inflammatory damage to ourselves. The great dilemma is that, when dying cancer cells are removed by phagocytes, the same intuitively “protective” action is provoked, as a number of suppressive factors that cause “immune tolerance” are produced by phagocytes, making the immune system oblivious of the residual cancer cells lingering in the body. This phagocyte-induced immune suppression is one of the main reasons for the emergence of immune escape variants and cancer recurrence even in the presence of common anti-cancer drugs. This phenomenon represents a “natural barrier” and a major hurdle in conventional cancer therapies that have not been appreciated or even been ignored.
How to break down the immune tolerance caused by phagocytes that have ingested dying cancer cells without causing severe autoimmune “collateral damage” is the overarching challenge that this project will address at both scientific and practical levels. We will seek to further uncover the fundamental mechanisms by which the immunosuppressive factors are produced by phagocytes after clearing dying cancer cells. Armed with the knowledge, we will then test the idea of blocking the production of these immune-inhibiting molecules in animal models of breast cancer to determine if the suppressed immune system can be reactivated to kill residual and even dormant cancer cells, and establish persistent immune memory that can recognize and eliminate recurring cancer cells. The long-term goal of the project is to identify appropriate ways to overcome the natural obstacle in standard cancer therapies. Our innovative idea, if validated, could lead to the development of truly creative strategies for breast cancer that are more efficacious, less toxic and longer-lasting in patients who receive conventional irradiation and chemotherapy.
In summary, current treatment regimens for breast cancer such as chemotherapy and irradiation intrinsically induce immuno-suppression, making it impossible to eliminate the residual cancer cells. Tumor regrowth and spread to distant sites inevitably emerge. Our preliminary studies have revealed that conventional approaches actually geminate and foster the residual cancer cells for the ultimate demise of the patient. Unorthodox ideas are urgently needed to circumvent this quagmire. Our proposed studies represent a novel quandary-breaking concept that could lead to truly innovative therapeutic strategies to override a natural immune barrier and take one strident step closer to an eventual “cure” for breast cancers.
How to break down the immune tolerance caused by phagocytes that have ingested dying cancer cells without causing severe autoimmune “collateral damage” is the overarching challenge that this project will address at both scientific and practical levels. We will seek to further uncover the fundamental mechanisms by which the immunosuppressive factors are produced by phagocytes after clearing dying cancer cells. Armed with the knowledge, we will then test the idea of blocking the production of these immune-inhibiting molecules in animal models of breast cancer to determine if the suppressed immune system can be reactivated to kill residual and even dormant cancer cells, and establish persistent immune memory that can recognize and eliminate recurring cancer cells. The long-term goal of the project is to identify appropriate ways to overcome the natural obstacle in standard cancer therapies. Our innovative idea, if validated, could lead to the development of truly creative strategies for breast cancer that are more efficacious, less toxic and longer-lasting in patients who receive conventional irradiation and chemotherapy.
In summary, current treatment regimens for breast cancer such as chemotherapy and irradiation intrinsically induce immuno-suppression, making it impossible to eliminate the residual cancer cells. Tumor regrowth and spread to distant sites inevitably emerge. Our preliminary studies have revealed that conventional approaches actually geminate and foster the residual cancer cells for the ultimate demise of the patient. Unorthodox ideas are urgently needed to circumvent this quagmire. Our proposed studies represent a novel quandary-breaking concept that could lead to truly innovative therapeutic strategies to override a natural immune barrier and take one strident step closer to an eventual “cure” for breast cancers.
系统生物学研究中心(威尼斯人
)