Alfredo Tartarone, Raffaele Conca, Alessandra Perrone, Rosa Lerose
In recent years, immunotherapy (I-O), following the introduction into clinical practice of several immune checkpoint inhibitors (ICIs), has revolutionized the treatment landscape of many types of cancer. To date, different ICIs, administered either as monotherapy or in combination with other agents, have been approved or are currently being tested for the treatment of more than 20 different cancer types, mainly in the metastatic setting. More recently, driven by the results achieved in advanced disease, I-O has expanded into the treatment of various tumors at earlier stages, showing promising results also in this context. I-O‑based combination regimens could be particularly effective in early-stage cancer due to different reasons such as the presence of a less immunosuppressive microenvironment, a more intact lymphatic-vascular architecture, a better T-cell fitness, a less tumor heterogeneity and resistance. We reviewed the role of I-O in early-stage non-small cell lung cancer, colorectal cancer, and melanoma with the aim of highlighting the potential advantages of I-O administration in this clinical setting. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science for English language peer-reviewed articles published until June 2026.