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Volume 3 Supplement 1

Abstracts of the Breast Cancer Immunotherapy Symposium (BRECIS): Sidra Symposia Series

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Pre-operative immunotherapy with tumor cryoablation (cryo) plus ipilimumab (ipi) induces potentially favorable systemic and intratumoral immune effects in early stage breast cancer (ESBC) patients

Journal for ImmunoTherapy of Cancer volume 3, Article number: O6 (2015) Cite this article

Background

In mice, cryo plus checkpoint blockade facilitates tumor antigen release, T-cell priming, and improved survival [1]. Here, we assess immune response in ESBC patients using biomarkers that have been attributed to clinical benefit following checkpoint blockade [2–5].

Methods

Women with ESBC were treated 7-10 days preceding mastectomy with either cryo (n=6), single-dose ipi at 10mg/kg (n=6), or cryo+ipi (n=6) [6]. From serial blood (baseline & 1-month post-mastectomy) and tumor (biopsy & mastectomy), fold-changes following cryo+ipi versus monotherapy were compared (Wilcoxon rank-sum) across the following measures: Ki67+ or ICOShi T-cells [2] and intratumoral T-effector/T-regulatory [3] cells by flow cytometry, plasma Th1/Th2 cytokines [4] (Meso Scale Discovery), and intratumoral T-cell expansion by immunohistochemistry [5] and T-cell receptor (TCR) deep sequencing (ImmunoSEQ) [5].

Results

Cryo+ipi generated greater increases in peripheral Ki67+CD4+ (p=0.05), Ki67+CD8+ (p=0.05), ICOShiCD4+ (p=0.005), and ICOShiCD8+ (p=0.005) cells. The intratumoral T-effector/regulatory ratio was higher following cryo+ipi, but only when Ki67-gated (p=.01). Cryo+ipi generated greater increases in IL-2 (p=.01), IFNγ (p=.06), and IL-5 (p=.09). Despite negligible intratumoral changes by immunohistochemistry, cryo+ipi generated more high-magnitude (~1000 amplicon) clonal expansions by TCR sequencing (medians: 52 v. 3 clones).

Conclusions

Cryo+ipi is associated with potentially favorable immunologic effects. Ki67-gating and TCR sequencing may identify intratumoral changes otherwise undetectable by flow or IHC.

References

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Authors and Affiliations

  1. Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    David B Page, Jianda Yuan, Zhiwan Dong, Stephen B Soloman, Sujata Patil, Clifford A Hudis, Jedd D Wolchok, Larry Norton & Heather L McArthur

  2. Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas, USA

    Adi Diab

Authors
  1. David B Page
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  2. Adi Diab
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  3. Jianda Yuan
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  4. Zhiwan Dong
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  5. Stephen B Soloman
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  6. Sujata Patil
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  7. Clifford A Hudis
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  8. Jedd D Wolchok
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  9. Larry Norton
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  10. Heather L McArthur
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Page, D.B., Diab, A., Yuan, J. et al. Pre-operative immunotherapy with tumor cryoablation (cryo) plus ipilimumab (ipi) induces potentially favorable systemic and intratumoral immune effects in early stage breast cancer (ESBC) patients. j. immunotherapy cancer 3 (Suppl 1), O6 (2015). https://doi.org/10.1186/2051-1426-3-S1-O6

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  • DOI: https://doi.org/10.1186/2051-1426-3-S1-O6

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