Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma

Journal of Translational Medicine

Research

Jennifer H. Yearley¹  Christopher Gibson¹  Haris Zahoor²  Zahra Rahman²  Rachel Dubner²  Cindy Sander³  John M. Kirkwood⁴  Uma N. M. Rao⁴  Ahmad A. Tarhini⁴ 

[1] Merck, Philadelphia, PA, USA;University of Pittsburgh Cancer Institute, 5150 Centre Avenue, 15232, Pittsburgh, PA, USA;University of Pittsburgh, Pittsburgh, PA, USA;University of Pittsburgh, Pittsburgh, PA, USA;University of Pittsburgh Cancer Institute, 5150 Centre Avenue, 15232, Pittsburgh, PA, USA;

关键词: Melanoma;    PD-1;    PD-L1;    Sentinel lymph node;   

DOI  :  10.1186/s12967-015-0678-7

 received in 2015-04-10, accepted in 2015-09-21,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCharacterization 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.MethodsPatients 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.ResultsTwenty-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 %).ConclusionsTumor-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.

【 授权许可】

CC BY   
© Tarhini et al. 2015