Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma.

Our results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance.