Cancer immune escape: implications for immunotherapy, Granada, Spain, October 3-5, 2011.

Abstract

Since 1985, a series of international conferences have taken place in Granada on the role of MHC class I antigens in cancer immune escape. This latest meetings, sponsored by the Ramon Areces Foundation, University of Granada, and University Hospital Virgen de las Nieves, were focused on research to improve our understanding of the molecular mechanisms of tumor evasion from immune surveillance and their implications for cancer immunotherapy. The outcome of complex interactions between the tumor and host immune system leads to either tumor progression or rejection. According to the theory of cancer immunosurveillance, if the immune system is able to keep cancer growth under control, the tumor can eventually be rejected. However, tumor cells can escape if the immunologic equilibrium is not maintained, leading to tumor growth and metastatic progression. It is becoming evident that malignant cells can develop sophisticated mechanisms of immune escape that limit the eVectiveness of immunomodulatory cancer treatments. Cancer immunotherapies designed to stimulate a powerful anti-tumor immune response by augmenting tumor immunogenicity and decreasing tumorinduced immunosuppression are being very actively introduced into the clinic setting. However, although the clinical responses observed with these immunotherapies have been encouraging, they remain far from satisfactory. The success of immunotherapy depends on overcoming cancer immune escape caused by a dysfunction of the host immune system and/or by the immunosuppressive eVect of the tumor microenvironment. One of the central mechanisms of immune evasion is associated with immune selection that favors the outgrowth of human leukocyte antigen (HLA) class I-negative tumor cells. In addition to intrinsic immune escape mechanisms, malignant cells induce activation of various immunosuppressive mechanisms in the tumor microenvironment to protect against immune reactivity. It is, therefore, very important and timely to explore new ways of overcoming cancer resistance to therapy and to improve our understanding of the molecular pathways involved in tumor-host interactions and tumor-induced suppression. This report summarizes the main topics addressed at the conference, including: the role of tumor cell immunogenicity and the tumor microenvironment; novel concepts and strategies in cancer immunotherapy; and the optimization of existing cancer vaccines and immunotherapy protocols.