Yanjun Hou1, Hiroaki Nitta2, Lai Wei3, Peter M Banks2, Anil V Parwani1, Zaibo Li4. 1. Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH. 2. Ventana Medical Systems, Inc, Tucson, AZ. 3. Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH. 4. Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH. Electronic address: Zaibo.Li@osumc.edu.
Abstract
BACKGROUND: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been extensively investigated in breast cancer. Programmed cell death 1 and its ligand (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However, the combination of TILs with PD-L1 expression has not been well studied in breast cancer. PATIENTS AND METHODS: A multi-color immunohistochemical multiplex assay simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole sections from 123 HER2-positive (HER2+) breast cancers, including 64 treated with anti-HER2 neoadjuvant therapy and subsequent resection. RESULTS: PD-L1 expression was identified in 88 cases (72%) including 21 (17%) in tumor cells and 67 (55%) in immune cells. PD-L1 expression was positively associated with high Nottingham grade, high nuclear grade, and a high level of CD8+ and CD163+ cells. Among the 64 patients who received neoadjuvant therapy, 39 had pathologic complete remission (pCR) and 25 had incomplete response. Multivariate analysis showed progesterone receptor negativity, HER2/chromosome 17 centromere (CEN17) ratio and intratumoral CD8+ cells were significantly associated with pCR. Furthermore, all patients with intratumoral CD8+ cells but no PD-L1 expression achieved pCR. CONCLUSION: Our data have shown that examination of intratumoral CD8+ cells together with PD-L1 expression proves useful in predicting response to anti-HER2 targeted therapy in patients with HER2+ breast cancer.
BACKGROUND: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been extensively investigated in breast cancer. Programmed cell death 1 and its ligand (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However, the combination of TILs with PD-L1 expression has not been well studied in breast cancer. PATIENTS AND METHODS: A multi-color immunohistochemical multiplex assay simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole sections from 123 HER2-positive (HER2+) breast cancers, including 64 treated with anti-HER2 neoadjuvant therapy and subsequent resection. RESULTS:PD-L1 expression was identified in 88 cases (72%) including 21 (17%) in tumor cells and 67 (55%) in immune cells. PD-L1 expression was positively associated with high Nottingham grade, high nuclear grade, and a high level of CD8+ and CD163+ cells. Among the 64 patients who received neoadjuvant therapy, 39 had pathologic complete remission (pCR) and 25 had incomplete response. Multivariate analysis showed progesterone receptor negativity, HER2/chromosome 17 centromere (CEN17) ratio and intratumoral CD8+ cells were significantly associated with pCR. Furthermore, all patients with intratumoral CD8+ cells but no PD-L1 expression achieved pCR. CONCLUSION: Our data have shown that examination of intratumoral CD8+ cells together with PD-L1 expression proves useful in predicting response to anti-HER2 targeted therapy in patients with HER2+ breast cancer.
Authors: A D Seidman; M N Fornier; F J Esteva; L Tan; S Kaptain; A Bach; K S Panageas; C Arroyo; V Valero; V Currie; T Gilewski; M Theodoulou; M E Moynahan; M Moasser; N Sklarin; M Dickler; G D'Andrea; M Cristofanilli; E Rivera; G N Hortobagyi; L Norton; C A Hudis Journal: J Clin Oncol Date: 2001-05-15 Impact factor: 44.544
Authors: D J Slamon; B Leyland-Jones; S Shak; H Fuchs; V Paton; A Bajamonde; T Fleming; W Eiermann; J Wolter; M Pegram; J Baselga; L Norton Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
Authors: Cecily P Vaughn; Scott D Zobell; Larissa V Furtado; Christine L Baker; Wade S Samowitz Journal: Genes Chromosomes Cancer Date: 2011-02-08 Impact factor: 5.006
Authors: Naiyer A Rizvi; Matthew D Hellmann; Alexandra Snyder; Pia Kvistborg; Vladimir Makarov; Jonathan J Havel; William Lee; Jianda Yuan; Phillip Wong; Teresa S Ho; Martin L Miller; Natasha Rekhtman; Andre L Moreira; Fawzia Ibrahim; Cameron Bruggeman; Billel Gasmi; Roberta Zappasodi; Yuka Maeda; Chris Sander; Edward B Garon; Taha Merghoub; Jedd D Wolchok; Ton N Schumacher; Timothy A Chan Journal: Science Date: 2015-03-12 Impact factor: 47.728
Authors: M F Press; M C Pike; V R Chazin; G Hung; J A Udove; M Markowicz; J Danyluk; W Godolphin; M Sliwkowski; R Akita Journal: Cancer Res Date: 1993-10-15 Impact factor: 12.701
Authors: H R Ali; S-E Glont; F M Blows; E Provenzano; S-J Dawson; B Liu; L Hiller; J Dunn; C J Poole; S Bowden; H M Earl; P D P Pharoah; C Caldas Journal: Ann Oncol Date: 2015-04-20 Impact factor: 32.976
Authors: Sang Byung Bae; Hyun Deuk Cho; Mee-Hye Oh; Ji-Hye Lee; Si-Hyong Jang; Soon Auck Hong; Junhun Cho; Sung Yong Kim; Sun Wook Han; Jong Eun Lee; Han Jo Kim; Hyun Ju Lee Journal: J Breast Cancer Date: 2016-09-23 Impact factor: 3.588
Authors: Deepak Mittal; Dipti Vijayan; Joost Neijssen; Joost Kreijtz; Maurice M J M Habraken; Hans Van Eenennaam; Andrea Van Elsas; Mark J Smyth Journal: Oncoimmunology Date: 2019-08-26 Impact factor: 8.110
Authors: Naoto T Ueno; Savitri Krishnamurthy; Jennifer A Wargo; Elizabeth A Mittendorf; Sangeetha M Reddy; Alexandre Reuben; Souptik Barua; Hong Jiang; Shaojun Zhang; Linghua Wang; Vancheswaran Gopalakrishnan; Courtney W Hudgens; Michael T Tetzlaff; James M Reuben; Takahiro Tsujikawa; Lisa M Coussens; Khalida Wani; Yan He; Lily Villareal; Anita Wood; Arvind Rao; Wendy A Woodward Journal: Cancer Immunol Res Date: 2019-05-01 Impact factor: 11.151
Authors: Preeti Kanikarla-Marie; Michael Lam; Alexey V Sorokin; Michael J Overman; Scott Kopetz; David G Menter Journal: Front Oncol Date: 2018-04-20 Impact factor: 6.244