To escape or not to escape innate immunity

Immunotherapy is a revolutionary approach to cancer treatment. However, many patients do not respond and the potential for serious side effects exists. Therapy often fails because tumor cells are not recognized (they turn invisible) or because of other immune suppressive mechanisms in the tumor microenvironment (TME) that further block therapy. To generate more effective responses to checkpoint immunotherapy it is critical to select patients that will benefit from therapy (the right patients) but also discover new compounds that can help fully unleash the immune response i.e or take out the “invisibility cloak” or block the other suppressive mechanisms that avoid the “good cops” from acting. Fior recently developed zebrafish Patient Derived Xenografts (zPDX) “Avatars” to perform a quick in vivo screen for personalized chemotherapy. During this work Fior uncovered an intricate and intriguing communication between tumor cells and zebrafish innate. Some human tumors can induce a suppressive TME, that blocks tumor rejection allowing tumors to thrive and progress whereas other tumor cells get rejected by the zebrafish innate immune cells (neutrophils and macrophages). This rejection occurs in just 4 days and tumor cells are completely wiped-out from the host. By taking advantage of this unique model the Fior Lab is focusing on understanding the molecular players involved in this rejection/ suppression process and discover new therapies to be combined with adaptive immunotherapy. Finally, another goal is to test if zebrafish “Avatars” can be used to select patients for immunotherapy.