Immunologic biomarkers as correlates of clinical response to cancer immunotherapy

摘要

Over the last few years, several newly developed immune-based cancer therapies have been shown to induce clinical responses in significant numbers of patients. As a result, there is a need to identify immune biomarkers capable of predicting clinical response. If there were laboratory parameters that could define patients with improved disease outcomes after immunomodulation, product development would accelerate, optimization of existing immune-based treatments would be facilitated and patient selection for specific interventions might be optimized. Although there are no validated cancer immunologic biomarkers that are predictive of clinical response currently in widespread use, there is much published literature that has informed investigators as to which markers may be the most promising. Population-based studies of endogenous tumor immune infiltrates and gene expression analyses have identified specific cell populations and phenotypes of immune cells that are most likely to mediate anti-tumor immunity. Further, clinical trials of cancer vaccines and other cancer directed immunotherapy have identified candidate immunologic biomarkers that are statistically associated with beneficial clinical outcomes after immune-based cancer therapies. Biomarkers that measure the magnitude of the Type I immune response generated with immune therapy, epitope spreading, and autoimmunity are readily detected in the peripheral blood and, in clinical trials of cancer immunotherapy, have been associated with response to treatment.