Abstract: The disclosure provides methods for predicting a positive clinical outcome for a cancer patient upon treatment with a 4-1BB agonistic agent, for assessing activity of such 4-1BB agonistic agent in a subject, preferably a cancer patient, and for selecting a dose of a 4-1BB agonistic agent for treating a disease, such as cancer. The disclosure also provides methods of treating cancer as well as uses of biomarkers and uses of kits for their detection.