Over the last decade, our understanding of how cancer cells interact with their microenvironment has grown exponentially. It has become evident that a complex interplay exists between malignant cells and benign host cells. The cancer cells and the “normal” cells, especially the immune compartment, undergo constant co-evolution to dynamically “shape” each other. Early attempts to utilize immune cells to favor anti-tumor responses date back more than a hundred years, when William Coley used bacteria to evoke immune responses in cancer patients, however, the results were controversial. Now, in the twenty-first century, “evading the immune system” has been recognized as a key hallmark of cancer.