Abstract
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.
Highlights
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
We present data which shows that tumor-associated PD-L1 expression is readily detectable within melanoma micrometastases in the SLN
Twenty-four patients where metastatic melanoma presence in the SLN was confirmed by Hematoxylin and eosin (H&E) review of the cut sections were included in the final analysis of PD-L1 expression
Summary
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. Higher expression levels of PD-L1 on tumors have been shown to correlate with poor prognosis in several malignant tumors including melanoma, esophagus, kidney, lung, and brain, pancreatic, ovarian and head and neck [8, 9, 12, 16, 25, 26]. These data illustrate a central role for the PD-1/PD-L1 axis in tumor immune escape and have led to the clinical targeting of PD-1 and PD-L1 as an antitumor strategy
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