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Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases.
Mod Pathol. 2015 Dec; 28(12):1535-44.MP

Abstract

Melanoma patients with sentinel lymph node metastases have variable 5-year survival rates (39-70%). The prognostic significance of tumor-infiltrating lymphocytes in sentinel lymph node metastases from such patients is currently unknown. Anti-PD-1/PD-L1 inhibitors have significantly improved clinical outcome in unresectable AJCC stage IIIC/IV metastatic melanoma patients, and are being trialed in the adjuvant setting in advanced stage disease, however, their role in early stage (sentinel lymph node positive) metastatic disease remains unclear. The aims of this study were to characterize, in sentinel lymph nodes, the subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumor PD-L1 expression as this may provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in sentinel lymph node positive metastatic melanoma patients. Sentinel lymph nodes containing metastatic melanoma from 60 treatment-naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 using immunohistochemistry on serial sections. The results were correlated with clinicopathologic features and outcome. Positive correlations between recurrence-free/overall survival with the number of CD3+ tumor-infiltrating lymphocytes (hazard ratio=0.36 (0.17-0.76), P=0.005; hazard ratio=0.29 (0.14-0.61), P=0.0005, respectively), the number of CD4+ tumor-infiltrating lymphocytes (hazard ratio=0.34 (0.15-0.77), P=0.007; hazard ratio=0.32 (0.14-0.74), P=0.005, respectively), and the number of CD8+ tumor-infiltrating lymphocytes (hazard ratio =0.42 (0.21-0.85), P=0.013; hazard ratio =0.32 (0.19-0.78), P=0.006, respectively) were observed. There was also a negative correlation with the number of peritumoral PD-1+ lymphocytes (hazard ratio=2.67 (1.17-6.13), P=0.016; hazard ratio=2.74 (1.14-6.76), P=0.019, respectively). Tumoral PD-L1 expression was present in 26 cases (43%) but did not correlate with outcome. The findings suggest that T-cell subsets in sentinel lymph node metastases can predict melanoma patient outcome. In addition, the relatively high number of PD-L1 positive sentinel lymph node melanoma metastases provides a rationale for anti-PD-1 therapy trials in sentinel lymph node positive melanoma patients, particularly those with peritumoral PD-1+ lymphocytes.

Authors+Show Affiliations

Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia.Merck Research Laboratories, Palo Alto, CA, USA.Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.Melanoma Institute Australia, North Sydney, NSW, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26403784

Citation

Kakavand, Hojabr, et al. "Tumor PD-L1 Expression, Immune Cell Correlates and PD-1+ Lymphocytes in Sentinel Lymph Node Melanoma Metastases." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 28, no. 12, 2015, pp. 1535-44.
Kakavand H, Vilain RE, Wilmott JS, et al. Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases. Mod Pathol. 2015;28(12):1535-44.
Kakavand, H., Vilain, R. E., Wilmott, J. S., Burke, H., Yearley, J. H., Thompson, J. F., Hersey, P., Long, G. V., & Scolyer, R. A. (2015). Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 28(12), 1535-44. https://doi.org/10.1038/modpathol.2015.110
Kakavand H, et al. Tumor PD-L1 Expression, Immune Cell Correlates and PD-1+ Lymphocytes in Sentinel Lymph Node Melanoma Metastases. Mod Pathol. 2015;28(12):1535-44. PubMed PMID: 26403784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases. AU - Kakavand,Hojabr, AU - Vilain,Ricardo E, AU - Wilmott,James S, AU - Burke,Hazel, AU - Yearley,Jennifer H, AU - Thompson,John F, AU - Hersey,Peter, AU - Long,Georgina V, AU - Scolyer,Richard A, Y1 - 2015/09/25/ PY - 2015/05/24/received PY - 2015/08/11/revised PY - 2015/08/29/accepted PY - 2015/9/26/entrez PY - 2015/9/26/pubmed PY - 2016/9/15/medline SP - 1535 EP - 44 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 28 IS - 12 N2 - Melanoma patients with sentinel lymph node metastases have variable 5-year survival rates (39-70%). The prognostic significance of tumor-infiltrating lymphocytes in sentinel lymph node metastases from such patients is currently unknown. Anti-PD-1/PD-L1 inhibitors have significantly improved clinical outcome in unresectable AJCC stage IIIC/IV metastatic melanoma patients, and are being trialed in the adjuvant setting in advanced stage disease, however, their role in early stage (sentinel lymph node positive) metastatic disease remains unclear. The aims of this study were to characterize, in sentinel lymph nodes, the subpopulations of lymphocytes that interact with metastatic melanoma cells and analyze their associations with outcome, and to determine tumor PD-L1 expression as this may provide a rational scientific basis for the administration of adjuvant anti-PD-1/PD-L1 inhibitors in sentinel lymph node positive metastatic melanoma patients. Sentinel lymph nodes containing metastatic melanoma from 60 treatment-naive patients were analyzed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 using immunohistochemistry on serial sections. The results were correlated with clinicopathologic features and outcome. Positive correlations between recurrence-free/overall survival with the number of CD3+ tumor-infiltrating lymphocytes (hazard ratio=0.36 (0.17-0.76), P=0.005; hazard ratio=0.29 (0.14-0.61), P=0.0005, respectively), the number of CD4+ tumor-infiltrating lymphocytes (hazard ratio=0.34 (0.15-0.77), P=0.007; hazard ratio=0.32 (0.14-0.74), P=0.005, respectively), and the number of CD8+ tumor-infiltrating lymphocytes (hazard ratio =0.42 (0.21-0.85), P=0.013; hazard ratio =0.32 (0.19-0.78), P=0.006, respectively) were observed. There was also a negative correlation with the number of peritumoral PD-1+ lymphocytes (hazard ratio=2.67 (1.17-6.13), P=0.016; hazard ratio=2.74 (1.14-6.76), P=0.019, respectively). Tumoral PD-L1 expression was present in 26 cases (43%) but did not correlate with outcome. The findings suggest that T-cell subsets in sentinel lymph node metastases can predict melanoma patient outcome. In addition, the relatively high number of PD-L1 positive sentinel lymph node melanoma metastases provides a rationale for anti-PD-1 therapy trials in sentinel lymph node positive melanoma patients, particularly those with peritumoral PD-1+ lymphocytes. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/26403784/Tumor_PD_L1_expression_immune_cell_correlates_and_PD_1+_lymphocytes_in_sentinel_lymph_node_melanoma_metastases_ L2 - https://doi.org/10.1038/modpathol.2015.110 DB - PRIME DP - Unbound Medicine ER -