Preoperative immune checkpoint inhibition and cryoablation in early-stage breast cancer

Comen, Elizabeth, Budhu, Sadna, Elhanati, Yuval, Page, David, Rasalan-Ho, Teresa, Ritter, Erika, Wong, Phillip, Plitas, George, Patil, Sujata, Brogi, Edi, Jochelson, Maxine, Bryce, Yolanda, Solomon, Stephen B, Norton, Larry, Merghoub, Taha, McArthur, Heather L (February 2024) Preoperative immune checkpoint inhibition and cryoablation in early-stage breast cancer. iScience, 27 (2). p. 108880. ISSN 2589-0042

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Abstract

Local cryoablation can engender systemic immune activation/anticancer responses in tumors otherwise resistant to immune checkpoint blockade (ICB). We evaluated the safety/tolerability of preoperative cryoablation plus ipilimumab and nivolumab in 5 early-stage/resectable breast cancers. The primary endpoint was met when all 5 patients underwent standard-of-care primary breast surgery undelayedly. Three patients developed transient hyperthyroidism; one developed grade 4 liver toxicity (resolved with supportive management). We compared this strategy with cryoablation and/or ipilimumab. Dual ICB plus cryoablation induced higher expression of T cell activation markers and serum Th1 cytokines and reduced immunosuppressive serum CD4+PD-1hi T cells, improving effector-to-suppressor T cell ratio. After dual ICB and before cryoablation, T cell receptor sequencing of 4 patients showed increased T cell clonality. In this small subset of patients, we provide preliminary evidence that preoperative cryoablation plus ipilimumab and nivolumab is feasible, inducing systemic adaptive immune activation potentially more robust than cryoablation with/without ipilimumab.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > cancer types
CSHL Authors:	Norton, Larry
Communities:	CSHL labs > Wigler lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	16 February 2024
Date Deposited:	20 Feb 2024 13:34
Last Modified:	20 Feb 2024 13:34
PMCID:	PMC10850740
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41437

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