Paolo Bossi, MD, University of Brescia, Brescia, Italy, discusses the development of resistance to immunotherapy in patients with primary cutaneous squamous cell carcinomas (cSCC), highlighting the clinical and molecular significance. Dr Bossi speaks on the Phase II I-TACKLE trial (NCT03666325) of pembrolizumab and cetuximab in patients with locally advanced/metastatic cSCC, which aims to tackle the development of resistance to immune checkpoint blockade. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.