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

Liu, Jing, Blake, Stephen J., Yong, Michelle C. R., Harjunpaa, Heidi, Ngiow, Shin Foong, Takeda, Kazuyoshi, Young, Arabella, O'Donnell, Jake S., Allen, Stacey, Smyth, Mark J. and Teng, Michele W. L. (2016) Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discovery, 6 12: 1382-1399. doi:10.1158/2159-8290.CD-16-0577


Author Liu, Jing
Blake, Stephen J.
Yong, Michelle C. R.
Harjunpaa, Heidi
Ngiow, Shin Foong
Takeda, Kazuyoshi
Young, Arabella
O'Donnell, Jake S.
Allen, Stacey
Smyth, Mark J.
Teng, Michele W. L.
Title Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease
Journal name Cancer Discovery   Check publisher's open access policy
ISSN 2159-8290
2159-8274
Publication date 2016-12-01
Sub-type Article (original research)
DOI 10.1158/2159-8290.CD-16-0577
Open Access Status Not yet assessed
Volume 6
Issue 12
Start page 1382
End page 1399
Total pages 18
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
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.

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. 1312This article is highlighted in the In This Issue feature, p. 1293.
Formatted 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.
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Document type: Journal Article
Sub-type: Article (original research)
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