Cancer Immunotherapy: Beyond Immune Checkpoint Blockade and Overcoming Resistance - ABSTRACT Support is requested for a Keystone Symposia conference entitled Cancer Immunotherapy: Beyond Immune Checkpoint Blockade and Overcoming Resistance, organized by Drs. James Allison, Andrea Schietinger, Antoni Ribas and Padmanee Sharma. The conference will be held in British Columbia, Canada from March 17–20, 2024. Immune checkpoint blockade therapy (ICT) has provided lasting cures for a subset of patients with specific cancers. Attempts to expand ICT toward other patients and cancers has revealed some of the limitations of ICT, particularly as monotherapies. This meeting will discuss some of those limitations, touching upon lessons learned from failed clinical trials, mechanisms of resistance to ICT, and new technologies which offer the promise of a more comprehensive understanding of the tumor-immune response. A strong emphasis will also be placed on exploring tumor-immunity beyond T cell biology. A better understanding of why immuno-oncology clinical trials have failed in the past is expected to better inform basic scientists on design of pre-clinical studies that may guide improved clinical trials that avoid the mistakes of the past. Further elucidation of the mechanisms through which cancers are either refractory to initial treatment with ICT or gain resistance over time should provide avenues to predict rationally designed combinatorial treatments from among the hundreds of thousands to millions of potential combinations. Finally, new technologies, including high dimensional spatiotemporal imaging and T cell engineering, provide new opportunities to expand our knowledge of immunology and therapeutic repertoire sometimes in unexpected ways. This meeting brings together scientists and clinicians from many aspects of tumor immunology to rethink the next steps in the evolution of cancer immunotherapy. It is expected to provide a springboard toward basic science discoveries and new, more effective therapies.