The concept of ‘iatrogenic resistance’: insights into mechanisms of induction of resistance to immune checkpoint blockade in combination immunotherapy

Immune checkpoint blockade has emerged as one of the most promising therapeutic strategies for cancer. Immune checkpoint inhibitors (ICIs), programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated protein-4 (CTLA-4), that have been approved for multiple tumor types have shown durable outcomes but only in a limited number of patients. Over the years, several mechanisms of resistance to currently used ICI therapy have been identified and utilized to develop better therapeutic approaches. However, many barriers to progress still exist and newer insights and tools are needed to overcome resistance to ICIs. Here, we provide a translational insight into some of these issues and associated mechanisms.

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