Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

person Daniele Fanale Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy info_outline Daniele Fanale, Lorena Incorvaia, Gaetana Rinaldi, Lidia Terruso, Giuseppe Badalamenti, Alessandra Cucinella, Mirna Swayden, Daniel Olive, Lidia Rita Corsini, Aurelia Guarini, Valerio Gristina, Luisa Castellana, Marco Bono, Viviana Bazan, Ignazio Ugo Carreca, Stefania Gori, Juan Iovanna, Antonio Russo

Authors person Daniele Fanale Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy info_outline Daniele Fanale, Lorena Incorvaia, Gaetana Rinaldi, Lidia Terruso, Giuseppe Badalamenti, Alessandra Cucinella, Mirna Swayden, Daniel Olive, Lidia Rita Corsini, Aurelia Guarini, Valerio Gristina, Luisa Castellana, Marco Bono, Viviana Bazan, Ignazio Ugo Carreca, Stefania Gori, Juan Iovanna, Antonio Russo Organizations Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy, Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy, Policlinico Giaccone, Palermo, Italy, Azienda Ospedaliera Universitaria "Paolo Giaccone", Palermo, Italy, Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France, Institut Paoli-Calmettes CRCM U1068, Marseille, France, University of Palermo, Palermo, Italy, Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; Medical Oncology Unit, Department of Surgical, Oncological, and Oral Sciences, University of Palermo, Palermo, Italy, Oncology Unit, Ospedale Sacro Cuore-don Calabria, Negrar, Italy, Inserm U624 Stress Cellulaire, Marseille, France, Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, PA, Italy Abstract Disclosures Research Funding Other Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Results: 16 out of 28 patients showed the presence of TILs in primary tumor, 10 of which brisk and 6 nonbrisk. The plasma PD-1 levels were analyzed in relation to the presence/absence of TILs (p = 0.022), brisk TILs versus nonbrisk/absent TILs (p = 0.014), and brisk vs nonbrisk vs absent TILs (p = 0.032). In particular, low plasma PD-1 levels have been shown to be associated with brisk TILs in primary melanoma, intermediate values with nonbrisk TILs, and high expression with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant association between the plasma PD-1 expression levels and overall survival (OS) depending on the absence or presence of TILs (brisk/nonbrisk), however the median survival of patients having brisk TILs was five months higher than other 2 groups of patients with absent and nonbrisk TILs, respectively. Conclusions: This work highlights, for the first time, the potential ability of using the plasma PD-1 levels to predict prognosis also in patients with metastatic melanoma at diagnosis for which it is not possible to identify the primary tumor.