The Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial Cancer

The abysmal outlook of urothelial cancer (UC) has changed with the introduction of immunotherapy. Still, many patients do not respond and distinctive biomarkers are currently lacking. The rise of this novel armamentarium of immunotherapy treatments, in combination with the complex biology of an immunological tumor response, warrants the development of a comprehensive framework that can provide an overview of important immunological processes at play in individual patients. To develop a comprehensive framework based on tumor- and host-specific parameters to understand immunotherapy response in UC. This framework can inform rational, biology-driven clinical trials and ultimately guide us toward individualized patient treatment. A literature review was conducted on UC immunotherapy, clinical trial data, and biomarkers of response to checkpoint inhibition. Here, we propose a UC immunogram, based on currently available clinical and translational data. The UC immunogram describes several tumor- and host-specific parameters that are required for successful immunotherapy treatment. These seven parameters are tumor foreignness, immune cell infiltration, absence of inhibitory checkpoints, general performance and immune status, absence of soluble inhibitors, absence of inhibitory tumor metabolism, and tumor sensitivity to immune effectors. Longitudinal integration of individual patient parameters may ultimately lead to personalized and dynamic immunotherapy, to adjust to the Darwinian forces that drive tumor evolution. Incorporating multiparameter biomarkers into quantitative predictive models will be a key challenge to integrate the immunogram into daily clinical practice. Here, we propose the urothelial cancer immunogram, a novel way of describing important immunological characteristics of urothelial cancer patients and their tumors. Seven characteristics determine the chance of having an immunological tumor response. Using this immunogram, we aim to better understand why some patients respond to immunotherapy and some do not, to ultimately improve anticancer therapy. Checkpoint inhibitors induce durable responses in a subset of urothelial cancer (UC) patients. A theoretical framework to understand immunotherapy response is warranted. Longitudinal integration of multiple parameters into the UC immunogram may ultimately lead to individualized immunotherapy to combat therapy resistance.