title: Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma.
abstract: BACKGROUND
  Characterization of PD-L1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes (SLN) is important to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy.
  
  
  METHODS
  Patients included had primary cutaneous melanoma, Breslow thickness of 2.01-4.0 or >4 mm with or without tumor ulceration (T3a, T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. The slides were separately evaluated by two pathologists (JY and CG). Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral and peritumoral locations, by utilizing two scoring methods.
  
  
  RESULTS
  Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by H&E review of the cut sections were included in the final analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2 mm. For three patients, the melanin content was too high to confidently assign a PD-L1 score. For the remaining 21 patients, all had some evidence of either intratumoral or peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD-L1 expression was: 0 % of tumor cells (3 pts, 14 %); <1 % (5 pts, 24 %); 1-10 % (6 pts, 29 %) and >10 % (7 pts, 33 %).
  
  
  CONCLUSIONS
  Tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN of the majority of patients. These results support the testing of a therapeutic role for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma micrometastases.
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA. tarhiniaa@upmc.edu.|University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. tarhiniaa@upmc.edu.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Tarhini
authors.affiliation: University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. zahoor@upmc.edu.
authors.forename: Haris
authors.initials: H
authors.lastname: Zahoor
authors.affiliation: Merck, Philadelphia, PA, USA. jennifer.yearley@merck.com.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Yearley
authors.affiliation: Merck, Philadelphia, PA, USA. christopher.gibson2@merck.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gibson
authors.affiliation: University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. rahman23@upmc.edu.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Rahman
authors.affiliation: University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. racheldubner2018@u.northwestern.edu.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dubner
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA. raounm@upmc.edu.|University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. raounm@upmc.edu.
authors.forename: Uma N M
authors.initials: UN
authors.lastname: Rao
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA. sandca@upmc.edu.
authors.forename: Cindy
authors.initials: C
authors.lastname: Sander
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA. kirkwoodjm@upmc.edu.|University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. kirkwoodjm@upmc.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D061206:Neoplasm Micrometastasis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000378:metabolism* / Q000628:therapy; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor