Preoperative immune checkpoint inhibition and cryoablation in early-stage breast cancer
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 e...
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| Vydané v: | iScience Ročník 27; číslo 2; s. 108880 |
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United States
Elsevier Inc
16.02.2024
Elsevier |
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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.
[Display omitted]
•Preoperative cryoablation plus ipilimumab and nivolumab is feasible in breast cancer•This therapy induces systemic adaptive immune activation in patients•This therapy is potentially more robust than cryoablation with/without ipilimumab
Health sciences; Oncology; Immunology |
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| AbstractList | 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. •Preoperative cryoablation plus ipilimumab and nivolumab is feasible in breast cancer•This therapy induces systemic adaptive immune activation in patients•This therapy is potentially more robust than cryoablation with/without ipilimumab Health sciences; Oncology; Immunology 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.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. 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-1 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. 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. [Display omitted] •Preoperative cryoablation plus ipilimumab and nivolumab is feasible in breast cancer•This therapy induces systemic adaptive immune activation in patients•This therapy is potentially more robust than cryoablation with/without ipilimumab Health sciences; Oncology; Immunology 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. |
| ArticleNumber | 108880 |
| Author | Patil, Sujata Brogi, Edi Bryce, Yolanda Plitas, George Norton, Larry Ritter, Erika Jochelson, Maxine Solomon, Stephen B. Merghoub, Taha McArthur, Heather L. Budhu, Sadna Page, David Rasalan-Ho, Teresa Elhanati, Yuval Comen, Elizabeth Wong, Phillip |
| Author_xml | – sequence: 1 givenname: Elizabeth surname: Comen fullname: Comen, Elizabeth email: comene@mskcc.org organization: Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 2 givenname: Sadna surname: Budhu fullname: Budhu, Sadna email: sab4028@med.cornell.edu organization: Ludwig Collaborative and Swim Across America Laboratory, Department of Pharmacology and Mayer Cancer Center, Weill Cornell Medicine, New York, NY, USA – sequence: 3 givenname: Yuval surname: Elhanati fullname: Elhanati, Yuval organization: Computational Oncology Service, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 4 givenname: David surname: Page fullname: Page, David organization: Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA – sequence: 5 givenname: Teresa surname: Rasalan-Ho fullname: Rasalan-Ho, Teresa organization: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 6 givenname: Erika surname: Ritter fullname: Ritter, Erika organization: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 7 givenname: Phillip surname: Wong fullname: Wong, Phillip organization: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 8 givenname: George surname: Plitas fullname: Plitas, George organization: Breast Surgery, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 9 givenname: Sujata surname: Patil fullname: Patil, Sujata organization: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 10 givenname: Edi surname: Brogi fullname: Brogi, Edi organization: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 11 givenname: Maxine surname: Jochelson fullname: Jochelson, Maxine organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 12 givenname: Yolanda surname: Bryce fullname: Bryce, Yolanda organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 13 givenname: Stephen B. surname: Solomon fullname: Solomon, Stephen B. organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 14 givenname: Larry surname: Norton fullname: Norton, Larry organization: Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 15 givenname: Taha surname: Merghoub fullname: Merghoub, Taha organization: Ludwig Collaborative and Swim Across America Laboratory, Department of Pharmacology and Mayer Cancer Center, Weill Cornell Medicine, New York, NY, USA – sequence: 16 givenname: Heather L. surname: McArthur fullname: McArthur, Heather L. email: heather.mcarthur@utsouthwestern.edu organization: Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA |
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