Tumor and systemic immune responses to preoperative (pre-op) cryoablation (cryo) plus immune therapy with ipilimumab (ipi) in early-stage breast cancer (ESBC).

Local/Regional Therapy
Session Type and Session Title: 
General Poster Session A: Local/Regional Therapy, Survivorship, and Health Policy
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 26; abstr 64)
David B. Page, Jianda Yuan, Arielle Ginsberg, Zhiwan Dong, Phillip Wong, Ryan Emerson, Janice S. Sung, Christopher Comstock, Stephen Barnett Solomon, Virgilio Sacchini, Monica Morrow, Edi Brogi, Elizabeth Ann Morris, Sujata Patil, Harlan Robins, Jedd D. Wolchok, Clifford A. Hudis, Larry Norton, James Patrick Allison, Heather L. McArthur; Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Institute, New York, NY; Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, New York, NY; Adaptive Biotechnologies, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; The University of Teaxas MD Anderson Cancer Center, Houston, TX

Abstract Disclosures


Background: In mice, tumor cryo plus immunologic checkpoint blockade generates tumor antigen release, proliferation of tumor-specific T-cells, and enhanced survival. We previously demonstrated in a pilot study that pre-op cryo+ipi is well tolerated in women with ESBC and did not delay standard of care surgical resection. Here, we analyze pilot study tissue and blood to explore immune response. Methods: 18 ESBC patients (pts) were treated with preop cryo (n=6), single-dose ipi 10mg/kg (n=6), or cryo+ipi (n=6). As a potential surrogate for tumor immunogenicity, baseline T-cell tumor infiltrating lymphocyte (TIL) density was evaluated by T-cell receptor quantitative DNA sequencing. We explored the systemic immune response to cryo and/or ipi using previously described laboratory measures including inducible costimulator (ICOS, a marker of activated CD4+ T-cells) and plasma interferon gamma (IFNγ, a cytokine associated with T-cell activity). Results: Of the 18 study pts, 13 pts had hormone receptor-positive (HR+) disease, 2 pts had HER2+ disease (both treated with ipi alone) and 3 pts had triple-negative (TN) disease (1 ipi alone and 2 cryo/ipi). Baseline TIL density was highly variable overall (range 2-30%), but higher in HER2+ and TN pts (median 15%) compared with HR+ pts (median 5%). Sustained >2-fold elevations in ICOS and IFNγ were observed in the majority of cryo+ipi pts 30 days following treatment (ICOS: 5/6 pts; IFNγ: 4/6 pts), but in the minority of ipi pts (ICOS: 2/6 pts; IFNγ: 2/6 pts) or cryo pts (ICOS: 0/6 pts; IFNγ: 0/6 pts). Sustained ICOS and IFNγ elevations were observed regardless of baseline TIL density. Conclusions: Cryo+ipi was more likely to induce systemic immune activation compared to cryo or ipi alone. These potentially beneficial immune effects were observed in both HR+ and HR- subtypes, as well as in tumors with low or high baseline TIL density. These data support further studies of cryo+ipi in ESBC across HR+ and HR- subtypes, as well as in tumors that do not appear immunogenic at baseline.