Background: Anti-PD1/PDL1 immunotherapy has demonstrated unprecedented clinical antitumor activity in patients with metastatic melanoma supporting planned testing as adjuvant therapy in patients with operable disease at high risk of recurrence and death. Characterization of PDL1 expression within clinically/radiologically negative but microscopically tumor positive sentinel lymph nodes is critical to our understanding of the relevance of this immune checkpoint pathway for adjuvant therapy.
Methods: Cut sections (5 µm) of sentinel lymph node from 25 patients reported positive for melanoma micrometastasis were included. H&E staining was performed, followed by PD-L1 immunohistochemical (IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3. Slides from 2 patients were also stained using an anti-HMB45/MelA protocol to better ascertain the presence and/or localization of melanoma lesions in the tissue in order to facilitate interpretation of the PD-L1 staining in those samples. The slides were separately evaluated by 2 pathologists. Samples containing metastatic melanoma lesions were scored separately for PD-L1 expression in intratumoral (including along tumor periphery but with clear tumor cell labeling) and peritumoral (expression external to tumor nodule in immediately surrounding tissue) locations. For intratumoral signal, attempts were made to classify the expression as tumor cell associated (T), non-tumor cell associated (NT), or both (T/NT). Scores were assigned using a 0-5 semiquantitative scale assessing prevalence of positive cells where 0 = negative, 1 = minimal or rare, 2 = low, 3 = moderate, 4 = high, and 5 = very high. Samples where melanin content was too high to confidently assign a PD-L1 score were specifically noted.
Results: Twenty patients where metastatic melanoma presence in regional sentinel nodes was confirmed by H&E review of the cut sections were included in the final analysis of PDL1 expression in the target population. Table 1 summarizes the study results. Except for samples where melanin content was too high to confidently assign a PD-L1 score, all SLNs examined demonstrated evidence of intratumoral and/or peritumoral PD-L1 expression.
Conclusions: PD-L1 expression is readily detectable intratumorally and/or peritumorally within melanoma micrometastases in the SLN. These results support the testing of a therapeutic role for PD1/PDL1 inhibition in the adjuvant therapy setting, targeting melanoma micrometastases.
Patient with SLN+ Tumor Associated Expression
PD-L1 Score / Tumor ---- PD-L1 Score / Peritumoral
1. 1 T, very weak ---- 1
2. 4, predominantly T, peripheral ---- 1
3. melanin confounds ---- 2
4. 0 ---- 2 (adjacent subcapsular sinus)
5. 4 T/NT---- 2
6. 2, predominantly NT ---- 3
7. 0 ---- 3 (adjacent subcapsular sinus)
8. 2.5, predominantly NT ---- 3
9. 4.5, predominantly T, weak ---- 2 (adjacent sinus)
10. melanin confounds ---- 0
11. 1 T ---- 2.5
12. 0* ---- 2
13. 1 T ---- 1
14. 2.5 NT ---- 2
15. 2 predominantly NT ---- 3
16. 1 T ---- 2
17. melanin confounds ---- 0
18. 1 ---- 1
19. 1 NT ---- 2.5
20. 2 T, melanin confounds ---- 2
*Very few tumor cells. In one region where a few tumor cells were present, a dense area of PD-L1 positivity was present directly adjacent but was impossible to say if all were non-tumor; this is interpreted as most likely.
Citation Format: Ahmad A. Tarhini, Jennifer A. Yearley, Christopher Gibson, Uma N. M. Rao, Cindy Sander, John M. Kirkwood. Tumor associated PDL1 expression pattern in microsopically tumor positive sentinel lymph nodes (SLN) in patients with melanoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A90.
- ©2015 American Association for Cancer Research.