Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease

J Liu, SJ Blake, MCR Yong, H Harjunpää, SF Ngiow… - Cancer discovery, 2016 - AACR
J Liu, SJ Blake, MCR Yong, H Harjunpää, SF Ngiow, K Takeda, A Young, JS O'Donnell
Cancer discovery, 2016AACR
Immunotherapy has recently entered a renaissance phase with the approval of multiple
agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities,
including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer
treatment. Although immunotherapy has begun to have success in advanced cancer
treatment, its scheduling and efficacy with surgery to treat earlier stages of cancer and
prevent distant metastases have not been systematically examined. Here, we have used two …
Abstract
Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer treatment. Although immunotherapy has begun to have success in advanced cancer treatment, its scheduling and efficacy with surgery to treat earlier stages of cancer and prevent distant metastases have not been systematically examined. Here, we have used two models of spontaneously metastatic breast cancers in mice to illustrate the significantly greater therapeutic power of neoadjuvant, compared with adjuvant, immunotherapies in the context of primary tumor resection. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood sampling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. These data now provide a strong rationale to extensively test and compare neoadjuvant immunotherapy in humans.
Significance: We demonstrate the significantly greater therapeutic efficacy of neoadjuvant, compared with adjuvant, immunotherapies to eradicate distant metastases following primary tumor resection. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood sampling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. Cancer Discov; 6(12); 1382–99. ©2016 AACR.
See related commentary by Melero et al., p. 1312.
This article is highlighted in the In This Issue feature, p. 1293
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