Jude Raj (Duke University)

Although cancer resistance remains a challenge for many anti-cancer drugs, immunotherapy is a recent advancement that has produced long-lasting, durable responses. These responses, however, are only seen in a subset of patients. To maximize efficacy and minimize resistance, many clinical trials are underway to combine immunotherapy with other cancer therapies. While these trials are ongoing, it is not clear how tumors will co-evolve to selective pressures imposed by both anti-cancer drugs and the immune system. It is conceivable that cancer cells may develop new mechanisms to evade immune recognition under the influence of new selective pressures exerted by drug therapies. Indeed, our preliminary data demonstrate that in diverse tumor types, the residual tumor cells that survive treatment with cutting edge targeted therapies simultaneously evade immunological surveillance. Here, we will leverage our expertise in flow-based CRISPR/Cas9 screening, a powerful technique that provides highly resolved mechanistic insights, to reveal the mechanisms controlling this phenomenon, thus revealing the foundational knowledge necessary to potentially engineer synergistic immune responses by modulating tumors’ therapeutic and immunological co-evolution.