Abstract
It has been eight years since the first immune checkpoint-blocking antibody, ipilimumab, was approved for metastatic malignant melanoma treatment by FDA in 2011. During this period, several other immune checkpoint blockers have been newly developed and approved for certain cancers, including malignant melanoma. However, there have been several concerns with some of these. The overall response rate did not exceed 30% in many cancers; although combination therapy with ipilimumab and nivolumab increased efficacy, immune-related adverse events also increased. This observation facilitated the reverse translational research (rTR) approach, using clinical specimens from treated patients to gradually elucidate the mechanism of resistance and biomarkers to select patients who can potentially benefit from immunotherapy. This has also promoted the development of novel combination therapies. In this review, immunological findings that highlight the resistance mechanisms of cancers against immune checkpoint blockers and the novel attempts to achieve a break-through will be discussed.
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