Only a minority of patients derives long-term benefit from immune checkpoint inhibitors (ICI), highlighting our incomplete understanding of the biological mechanisms of anti-tumor immune responses.

Primary resistance could be the result of inadequate patient selection. Current modalities and timing of ICI-based combination should be reconsidered, to induce a responsive, inflamed tumor microenvironment.

Acquired resistance implies adaptive changes in the cancer–immune system crosstalk. For a deeper insight of these changes and the development of tailored treatment strategies, dedicated translational research using longitudinal samples is essential.