Immuno-oncology, which leverages the body's own immune system to fight cancer, is a true medical revolution. But to date, these therapies have only targeted one of the two arms of the immune system: the adaptive immune system. This is the arm that contains T cells, B cells, and antibodies and is what we generally think of when talking about immunity. But the second arm, the innate immune system, is equally important, as it mounts a fast-acting, non-specific immune response to a board range of invaders. Importantly, some cancers co-opt the innate immune system and use it as a shield against attacks by the adaptive immune system. In today's episode, host Lauren Richardson (@lr_bio) is joined by Dr. Willem Mulder (@WillemNANO), Professor at the Icahn School of Medicine at Mt. Sinai, to discuss a new approach to immuno-oncology that engages both arms of the immune system. This method uses engineered, synthetic, nano-scale "germs" to activate the innate immune system, and which works in combination with T cell-activating therapies to destroy cancer cells, even leading to complete tumor remission in mice. The conversation covers how these synthetic germs were developed from an early vaccine to tuberculosis, how they influence immune cell activity, their potential for treating cancer and an array of other conditions, and what is needed to take them out of the lab and into the clinic. Dr. Willem Mulder is a Professor at the Icahn School of Medicine at Mt. Sinai, Eindhoven University of Technology, and  Radboud University Medical Center and is a co-founder of Trained Therapeutix Discovery. He joins host Lauren Richardson to discuss the results and implications of the article "Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition" by Bram Priem, Mandy M.T. van Leent, Abraham J.P. Teunissen, Alexandros Marios Sofias, Vera P. Mourits, Lisa Willemsen, Emma D. Klein, Roderick S. Oosterwijk, Anu E. Meerwaldt, Jazz Munitz, Geoffrey Pre ́vot, Anna Vera Verschuur, Sheqouia A. Nauta, Esther M. van Leeuwen, Elizabeth L. Fisher, Karen A.M. de Jong, Yiming Zhao, Yohana C. Toner, Georgios Soultanidis, Claudia Calcagno, Paul H.H. Bomans, Heiner Friedrich, Nico Sommerdijk, Thomas Reiner, Raphae ̈l Duivenvoorden, Eva Zupancic, Julie S. Di Martino, Ewelina Kluza, Mohammad Rashidian, Hidde L. Ploegh, Rick M. Dijkhuizen, Sjoerd Hak, Carlos Pe ́ rez-Medina, Jose Javier Bravo-Cordero, Menno P.J. de Winther, Leo A.B. Joosten, Andrea van Elsas, Zahi A. Fayad, Alexander Rialdi, Denis Torre, Ernesto Guccione, Jordi Ochando, Mihai G. Netea, Arjan W. Griffioen, and Willem J.M. Mulder, published in Cell. For more on the innate immune system, also check out "Journal Club: Why do only some people get severe COVID-19?" and "Journal Club: How to Win an Evolutionary Arms Race"