Immune escape mechanisms of tumors and their impact for immunotherapies
Despite the recent success of different immunotherapeutic strategies, such as the use of antibodies directed against checkpoints as well as adoptive T cell therapy, the response of tumor patients is still limiting. This attributes to the escape of tumor cells from immune surveillance and the development of acquired resistances during therapy. Since different evasion and resistance mechanisms limit the efficacy of immunotherapies, overcoming these escape mechanisms is a great challenge and might lead to a better clinical outcome of patients. The strategies of tumors evading immune surveillance include alterations in classical and non-classical HLA class I antigens as well as in checkpoint molecules, like PD-L1 and B7H4. This could be due to structural alterations, which are a rare event or deregulation of various immune modulatory molecules mediated at the transcriptional, epigenetic, posttranscriptional as well as posttranslational level. A better understanding of the mechanisms might allow the selections for the appropriate (immuno)therapy as well as to novel therapeutic strategies to revert the escape thereby increasing immunorecognition of tumor cells.
Professor Dr. Barbara Seliger is the Director of the Institute for Medical Immunology at the Martin-Luther-University Halle-Wittenberg, in Halle, Germany, Director of a FOCIS Center of Excellence, member of the World Immunoscore and SITC biomarker initiatives. In addition she is head of the work group for “Tumor immunology” of the German Society of Immunology. Prof. Seliger’s research team studies the molecular events associated with immune escape of tumors, the role of the tumor micro-environment and immune cell subpopulations for tumor development and therapy resistance. In addi-tion, her laboratory is involved in optimization and monitoring immunotherapies and in the characteri-zation of biomarkers allowing the prediction of their success. Recently, she became interested in the identification, functional characterization and clinical relevance of immune regulatory microRNAs and RNA-binding proteins as their implementation as therapeutic tools as well as in the role of the tumor and immune cell metabolism in immune surveillance and its modulation as novel therapeutic option alone or in combination with targeted or immunotherapies.