A Pilot Study of Preoperative Single-Dose Ipilimumab and/or Cryoablation in Women with Early-Stage Breast Cancer with Comprehensive Immune Profiling

被引：187

作者：

McArthur, Heather L. ^{[1
]}

Diab, Adi ^{[2
]}

Page, David B. ^{[1
]}

Yuan, Jianda ^{[1
]}

Solomon, Stephen B. ^{[1
]}

Sacchini, Virgilio ^{[1
]}

Comstock, Christopher ^{[1
]}

Durack, Jeremy C. ^{[1
]}

Maybody, Majid ^{[1
]}

Sung, Janice ^{[1
]}

Ginsberg, Arielle ^{[1
]}

Wong, Phillip ^{[1
]}

Barlas, Afsar ^{[1
]}

Dong, Zhiwan ^{[1
]}

Zhao, Chunjun ^{[1
]}

Blum, Brian ^{[1
]}

Patil, Sujata ^{[1
]}

Neville, Deirdre ^{[1
]}

Comen, Elizabeth A. ^{[1
]}

Morris, Elizabeth A. ^{[1
]}

Kotin, Alan ^{[1
]}

Brogi, Edi ^{[1
]}

Wen, Y. Hannah ^{[1
]}

Morrow, Monica ^{[1
]}

Lacouture, Mario E. ^{[1
]}

Sharma, Padmanee ^{[2
]}

Allison, James P. ^{[2
]}

Hudis, Clifford A. ^{[1
]}

Wolchok, Jedd D. ^{[1
]}

Norton, Larry ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[2] MD Anderson Canc Ctr, Houston, TX USA

来源：

CLINICAL CANCER RESEARCH | 2016年 / 22卷 / 23期

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY T-CELLS; CTLA-4; BLOCKADE; METASTATIC MELANOMA; PROGNOSTIC VALUE; PD-1; CHEMOTHERAPY; EXPRESSION; NIVOLUMAB; SURVIVAL;

D O I：

10.1158/1078-0432.CCR-16-0190

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab-mediated immune modulation in women with operable breast cancer. Experimental Design: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activation were performed on peripheral blood and tumor. Results: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67(+)) CD4(+) and CD8(+) T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. Conclusions: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy. (C) 2016 AACR.

引用

页码：5729 / 5737

页数：9

共 37 条

[1] Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].

Adams, Sylvia ;

Gray, Robert J. ;

Demaria, Sandra ;

Goldstein, Lori ;

Perez, Edith A. ;

Shulman, Lawrence N. ;

Martino, Silvana ;

Wang, Molin ;

Jones, Vicky E. ;

Saphner, Thomas J. ;

Wolff, Antonio C. ;

Wood, William C. ;

Davidson, Nancy E. ;

Sledge, George W. ;

Sparano, Joseph A. ;

Badve, Sunil S. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+

[2] Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases [J].

Akdis, Muebeccel ;

Burgler, Simone ;

Crameri, Reto ;

Eiwegger, Thomas ;

Fujita, Hiroyuki ;

Gomez, Enrique ;

Klunker, Sven ;

Meyer, Norbert ;

O'Mahony, Liam ;

Palomares, Oscar ;

Rhyner, Claudio ;

Quaked, Nadia ;

Schaffartzik, Anna ;

Van De Veen, Willem ;

Zeller, Sabine ;

Zimmermann, Maya ;

Akdis, Cezmi A. .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2011, 127 (03) :701-U317

[3] PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].

Ansell, Stephen M. ;

Lesokhin, Alexander M. ;

Borrello, Ivan ;

Halwani, Ahmad ;

Scott, Emma C. ;

Gutierrez, Martin ;

Schuster, Stephen J. ;

Millenson, Michael M. ;

Cattry, Deepika ;

Freeman, Gordon J. ;

Rodig, Scott J. ;

Chapuy, Bjoern ;

Ligon, Azra H. ;

Zhu, Lili ;

Grosso, Joseph F. ;

Kim, Su Young ;

Timmerman, John M. ;

Shipp, Margaret A. ;

Armand, Philippe .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319

[4] Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial [J].

Carthon, Bradley C. ;

Wolchok, Jedd D. ;

Yuan, Jianda ;

Kamat, Ashish ;

Tang, Derek S. Ng ;

Sun, Jingjing ;

Ku, Geoffrey ;

Troncoso, Patricia ;

Logothetis, Christopher J. ;

Allison, James P. ;

Sharma, Padmanee .

CLINICAL CANCER RESEARCH, 2010, 16 (10) :2861-2871

[5] Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer [J].

Denkert, Carsten ;

Loibl, Sibylle ;

Noske, Aurelia ;

Roller, Marc ;

Mueller, Berit Maria ;

Komor, Martina ;

Budczies, Jan ;

Darb-Esfahani, Silvia ;

Kronenwett, Ralf ;

Hanusch, Claus ;

von Toerne, Christian ;

Weichert, Wilko ;

Engels, Knut ;

Solbach, Christine ;

Schrader, Iris ;

Dietel, Manfred ;

von Minckwitz, Gunter .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (01) :105-113

[6] Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme [J].

Di Giacomo, Anna Maria ;

Calabro, Luana ;

Danielli, Riccardo ;

Fonsatti, Ester ;

Bertocci, Erica ;

Pesce, Isabella ;

Fazio, Carolina ;

Cutaia, Ornella ;

Giannarelli, Diana ;

Miracco, Clelia ;

Biagioli, Maurizio ;

Altomonte, Maresa ;

Maio, Michele .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2013, 62 (06) :1021-1028

[7] Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study [J].

Dieci, M. V. ;

Criscitiello, C. ;

Goubar, A. ;

Viale, G. ;

Conte, P. ;

Guarneri, V. ;

Ficarra, G. ;

Mathieu, M. C. ;

Delaloge, S. ;

Curigliano, G. ;

Andre, F. .

ANNALS OF ONCOLOGY, 2014, 25 (03) :611-618

[8] ICOS co-stimulatory receptor is essential for T-cell activation and function [J].

Dong, C ;

Juedes, AE ;

Temann, UA ;

Shresta, S ;

Allison, JP ;

Ruddle, NH ;

Flavell, RA .

NATURE, 2001, 409 (6816) :97-101

[9] Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial [J].

Eggermont, Alexander M. M. ;

Chiarion-Sileni, Vanna ;

Grob, Jean-Jacques ;

Dummer, Reinhard ;

Wolchok, Jedd D. ;

Schmidt, Henrik ;

Hamid, Omid ;

Robert, Caroline ;

Ascierto, Paolo A. ;

Richards, Jon M. ;

Lebbe, Celeste ;

Ferraresi, Virginia ;

Smylie, Michael ;

Weber, Jeffrey S. ;

Maio, Michele ;

Konto, Cyril ;

Hoos, Axel ;

de Pril, Veerle ;

Gurunath, Ravichandra Karra ;

de Schaetzen, Gaetan ;

Suciu, Stefan ;

Testori, Alessandro .

LANCET ONCOLOGY, 2015, 16 (05) :522-530

[10]

Emens LA, 2015, AACR ANN M PHIL PA A

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