Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets.
The expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 68 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort. Our primary endpoint was to estimate the prevalence of PD-L1 expression and its prognostic impact in metastatic pRCC. Secondary endpoints included the evaluation of other immune markers (PD-1, PD-L2, and LAG-3) and their association with PD-L1. We also assessed angiogenic markers and their association with PD-L1.
Overall, 27.9 % of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.6 %), PD-1 and LAG-3 were positive in 17.6 % and 19.1 % respectively. None of these markers was correlated with PD-L1 expression. 66 % (45/68) expressed at least one immune marker, and 43 % (29/68) were "double-positive", as they expressed both immune and angiogenic markers. OS was significantly shorter for patients with PD-L1 positive pRCC. A multivariate analysis confirmed a significant association between PD-L1 expression and shorter overall survival (HR = 4.0, p = 0.01).
These results reinforce clinical data on the expected benefit of ICI in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in this multicenter cohort.
European journal of cancer (Oxford, England : 1990). 2024 May 13 [Epub ahead of print]
Jérémie Naffrichoux, Pierre Poupin, William Pouillot, Claude Linassier, Nathalie Rioux-Leclercq, Manon De Vries-Brilland, Loïc Mourey, Brigitte Laguerre, Stéphane Oudard, Marine Gross-Goupil, Coralie Mousset, Gwenaelle Gravis, Frédéric Rolland, Laura Moise, Sheik Emambux, Cécile Vassal, Sylvie Zanetta, Nicolas Penel, Laurence Albiges, Gaëlle Fromont, Mathilde Cancel
Department of Medical Oncology, University Hospital, Tours, France., INSERM CIC 1415, University Hospital, Tours, France., Department of Pathology, University Hospital, Tours, France., Department of Pathology, Pontchaillou University Hospital, Rennes, France., Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Angers, France., Department of Medical Oncology, IUCT Oncopole, Toulouse, France., Department of Medical Oncology, Eugène Marquis Cancer Center, Rennes, France., Department of Medical Oncology, Georges Pompidou Hospital, University Paris Cité, Paris, France., Department of Medical Oncology, Saint-André University Hospital, Bordeaux, France., Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France., Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France., Department of Medical Oncology, Centre François Baclesse, Caen, France., Department of Medical Oncology, La Milétrie University Hospital, Poitiers, France., Department of Medical Oncology, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France., Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France., Lille University and Department of Medical Oncology, Centre Oscar Lambret, Lille, France., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Pathology, University Hospital, Tours, France; INSERM UMR 1069, N2COx, Tours University, Tours, France., Department of Medical Oncology, University Hospital, Tours, France; INSERM UMR 1069, N2COx, Tours University, Tours, France. Electronic address: .