title: PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.
abstract: Programmed death 1 ligand 1 (PD-L1) is an immune regulatory molecule that limits antitumor immune activity. Targeting of PD-L1 and other immune checkpoint proteins has shown therapeutic activity in various tumor types. The expression of PD-L1 and its correlation with response to neoadjuvant chemotherapy in breast cancer has not been studied extensively. Our goal was to assess PD-L1 expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. Pretreatment biopsies from 105 patients with breast cancer from Yale New Haven Hospital that subsequently received neoadjuvant chemotherapy were assessed for PD-L1 protein expression by automated quantitative analysis with a rabbit monoclonal antibody (E1L3N) to the cytoplasmic domain of PD-L1. In addition, tumor-infiltrating lymphocytes (TIL) were assessed on hematoxylin and eosin slides. PD-L1 expression was observed in 30% of patients, and it was positively associated with hormone-receptor-negative and triple-negative status and high levels of TILs. Both TILs and PD-L1 measured in the epithelium or stroma predicted pathologic complete response (pCR) to neoadjuvant chemotherapy in univariate and multivariate analyses. However, because they are strongly associated, TILs and PD-L1 cannot both be included in a significant multivariate model. PD-L1 expression is prevalent in breast cancer, particularly hormone-receptor-negative and triple-negative patients, indicating a subset of patients that may benefit from immune therapy. Furthermore, PD-L1 and TILs correlate with pCR, and high PD-L1 predicts pCR in multivariate analysis.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Hallie
authors.initials: H
authors.lastname: Wimberly
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Kurt
authors.initials: K
authors.lastname: Schalper
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts.
authors.forename: Herbert
authors.initials: H
authors.lastname: Haack
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Silver
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Christian
authors.initials: C
authors.lastname: Nixon
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Veerle
authors.initials: V
authors.lastname: Bossuyt
authors.affiliation: Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Lannin
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut. david.rimm@yale.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D009363:Neoplasm Proteins