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Yvonne Mondorf, Marie Mikuteit, Philipp Ivanyi, Christine Stöhr, Edwin Herrmann, Iris Polifka, Abbas Agaimy, Lutz Trojan, Philipp Ströbel, Frank Becker, Christian Wülfing, Peter Barth, Michael Stöckle, Michael Staehler, Christian G. Stief, Axel Haferkamp, Markus Hohenfellner, Stephan Macher-Göppinger, Bernd Wullich, Joachim Noldus, Frederik C. Roos, Bernhard Walter, Wolfgang Otto, Maximilian Burger, Andres Jan Schrader, Arndt Hartmann, Sandra Steffens, Franziska Erlmeier, Walburgis Brenner

• \(\bf Introduction:\) Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC). \(\bf Methods:\) The patients’ sample collection was a joint collaboration of the PANZAR consortium. Patients’ medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases. \(\bf Results:\) PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2− compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS. \(\bf Discussion/Conclusion:\) PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches.