Patients with melanoma, the most concerning form of skin cancer in which pigment-producing cells start to grow out of control, can benefit from existing immunotherapies, but by far not all of them do. More than 50% of patients do not respond to current immunotherapy drugs and among those who initially respond, many become resistant to the drugs’ effects. Thus, besides developing more effective immunotherapies, doctors need to be able to determine which patients respond well at the start of treatments and, which ones keep or stop responding in order to make the best treatment decisions. Because cancerous skin lesions of melanoma patients are easily accessible, an effective way to eradicate them could be to apply immunotherapies locally, instead of systemically infusing them into the blood circulation. Also, monitoring the immune system’s reaction to the therapy right at the tumor site, by sensitively and continuously measuring different biomarkers that signal the intended immune cell activation and a desirable inflammatory response, could enable better and more personalized patient care.