Targeting Functionality of Cancer Cell-Derived Extra cellular vesicles to Immune Cells of the Tumor Microenvironment

Abstract

In most cases, cancer cells cannot proliferate alone. They receive support form stromal cells and recruit and reprogram non-malignant immune cells not to damage the cancer cells but to support the tumor growth. Classical Hodgkin lymphoma (cHL) is a good example, as its growth critically depends on tumor-supporting immune cells. The affected lymphoid tissue contains very few disseminated malignant Hodgkin- and Reed-Sternberg (H-RS) cells, which are outnumbered by a massive infiltrate of lymphocytes, fibroblasts and innate immune cells. [1]. The H-RS cells need this environment to survive and proliferate because they are usually not detectable in the peripheral blood and they have difficulties to grow in immune-deficient mice [2]. H-RS cells manipulate the bystander cells for better development of their malignant phenotype and evasion of the host defense [3]. Among the infiltrated immune cells, the eosinophils and mast cells play an important role and their cell count indicates a negative prognostic feature [4,5]. In vitro, the direct interaction with cancer cells communicates survival in cancer cells and the production of cancersupporting factors in immune cells. In the last years, extracellular vesicles (EVs) emerged as important vehicles to shuttle between different the cell types and communicate as a surrogate cellular crosstalk in trans [6,7].