Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar CD8+ Tcell density and PD-L1 protein expression on immune cells as compared to conventional UC

Myriam Kossaï (1, 2, 3, 4) , Camélia Radulescu (1, 2) , Julien Adam (5, 6) , Anaïs Dziegielewski (1, 2) , Nicolas Signolle (7, 8, 9) , Mathilde Sibony (10) , Thierry Lebret (1, 2) , Yves Allory (11, 12) , Mathieu Rouanne (1, 2, 13)

1 Hôpital Foch [Suresnes]
2 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
3 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
4 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
5 Centre hospitalier Saint-Joseph [Paris]
6 INTIM - Immunologie intégrative des tumeurs et immunothérapie des cancers
7 IGR - Institut Gustave Roussy
8 Université Paris-Saclay
9 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
10 Hôpital Cochin [AP-HP]
11 Institut Curie [Paris]
12 Biologie Cellulaire et Cancer
13 ITIC - Immunologie anti-tumorale et immunothérapie des cancers

Background: Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Methods: Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n=32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n=30). Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8+ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% P=0.18), CK20 (59% vs 36% P=0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, P<0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, P<0.05) and p63 (41% vs 80%, P<0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (P=0.9). PD-L1 expression on IC was similar compared to conventional UC (P=0.3). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.

Mots clés: Molecular subtype; Plasmacytoid variant; Tumor-infiltrating lymphocytes; Urothelial carcinoma

Domaines: Sciences du Vivant [q-bio]

Myriam Kossaï, Camélia Radulescu, Julien Adam, Anaïs Dziegielewski, Nicolas Signolle, et al.. Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar CD8+ Tcell density and PD-L1 protein expression on immune cells as compared to conventional UC. Urologic Oncology: Seminars and Original Investigations, 2022, 40 (1), pp.12.e1-12.e11. ⟨10.1016/j.urolonc.2021.07.014⟩. ⟨hal-03554197⟩