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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


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 [25].


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].


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).


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


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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).

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