Toward the identifi cation of genetic determinants of responsiveness to cancer immunotherapy

Abstract

For a long time, the lack of a human-centered translational approach to tumor immunology has led to the accumulation of a multitude of disjointed clinical and basic researches, followed by a disharmonic growth of scientifi c knowledge. The huge amount of conjectural hypotheses has competitively interfered with the few evidence-based concepts generated by studies conducted in humans, resulting in several clinical failures and some ‘mysterious’ successes. During the last few years, refi ned immunotherapies have been shown to induce clinical response and/or improve survival in a signifi cant proportion of cancer patients. Pari passu, high- throughput approaches applied to the analysis of tumor specimens have unveiled unexpected and paradoxical relations between cancer and the immune system. Such studies have described a cancer immune phenotype typifi ed by better prognosis and increased responsiveness to immunotherapeutic approaches. Whether the favorable cancer immune phenotype is dictated by the intrinsic genetics of the tumor or by the genetic makeup of the individual bearing the disease is presently unclear. Here, we focus on molecular biomarkers derived from genomic and genetic studies to summarize the recent advances in our understanding of the mechanisms associated with distinct outcomes in the context of cancer immunotherapy.