Immunotherapy using checkpoint inhibitors has changed the way we treat several aggressive cancers such as melanoma, non-small cell lung and head & neck cancers, among others, with durable responses achieved in the metastatic setting. However, unfortunately, the vast majority of patients do not respond to checkpoint inhibition therapy and a minority of patients, who do respond to treatment, develop secondary resistance and experience relapse by mechanisms still inadequately understood. Emerging evidence shows that alterations in multiple signaling pathways are involved in primary and/or secondary resistance to checkpoint inhibition. In this review we discuss how selected cancer-cell autonomous cues may influence the outcome of cancer immunotherapy, particularly immune checkpoint inhibition.
Keywords: Acquired resistance; BRAF; EGFR pathway; HIPPO pathway; Immune checkpoint; Immunotherapy; Intrinsic resistance; JAK1; JAK2; PI3K/AKT/mTOR pathway; Wnt/β-Catenin pathway.