Neodjuvant Cancer Immunotherapy

Immune checkpoint inhibition has revolutionized the management of patients with advanced malignancies by inducing durable tumor control and improving overall survival. In addition, checkpoint inhibitors are now an important pillar in the management of high-risk early-stage malignancies when administered adjuvantly, including melanoma. Because broad and effective immune activation depends on the immune system being exposed to a breadth of antigens, it is hypothesized that checkpoint inhibition in early-stage melanoma may be more effective when the drug is administered neoadjuvantly, whilst the tumor is still present, rather than adjuvantly, after complete resection (see Figure).

The recent trials that were the first to test neoadjuvant immune checkpoint inhibition support this hypothesis by virtue of the extraordinary high pathologic response observed, which was associated with almost no recurrences.

Neoadjuvant therapies provide an unparalleled translational research opportunity to explore gene expression signatures associated with response and to understand molecular mechanisms of resistance. This is a unique opportunity for reverse translation; designing novel experiments utilizing tissue specimens collected at lymph node dissection after neoadjuvant treatment, correlating these results with accurate and homogeneous clinical data, and using this information to select therapies in the clinic or in trials that are more likely to improve patient outcome.

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