Arthur Bauer1,2, Niklas Gebauer3, Juliana Knief4, Lars Tharun5, Nele Arnold6, Armin Riecke1, Konrad Steinestel2, Hanno M Witte7,8,9. 1. Department of Hematology and Oncology, Federal Armed Forces Hospital Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany. 2. Institute of Pathology and Molecular Pathology, Federal Armed Forces Hospital Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany. 3. Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. 4. Institute of Pathology, Marienkrankenhaus Hamburg, Alfredstraße 9, 22087, Hamburg, Germany. 5. Institute of Pathology, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. 6. Department of ENT, Federal Armed Forces Hospital Hamburg, Lesserstraße 180, 22049, Hamburg, Germany. 7. Department of Hematology and Oncology, Federal Armed Forces Hospital Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany. hanno.witte@uni-ulm.de. 8. Institute of Pathology and Molecular Pathology, Federal Armed Forces Hospital Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany. hanno.witte@uni-ulm.de. 9. Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. hanno.witte@uni-ulm.de.
Abstract
BACKGROUND: In salivary gland carcinomas (SGC), there is only a small fraction of entities that appears to profit from immune checkpoint inhibition (ICI). Recent findings connected the activation of adenosine-signaling with a tolerogenic microenvironment. Therefore, the inhibition of adenosine pathway markers (CD39 and/or CD73) can augment ICI and/or display a novel immunotherapeutic strategy beyond ICI. Here, we assessed the immuno-histochemical expression of CD39 and CD73 across a wide spectrum of SGCs. METHODS: In total, 114 patients with SGCs consecutively diagnosed between 2001 and 2021 were assessed for clinicopathological baseline characteristics and underwent confirmatory histopathological review. Immunohistochemical expression levels of CD39 and CD73 were assessed by applying the tumor proportion score (TPS) and the immune proportional score (IPS) comparable to PD-L1 expression analysis in routine clinical practice. Additionally, findings were correlated with PD-L1 expression levels. RESULTS: The median age was 60.6 and 51.8% patients were female. The cohort covered a spectrum of eight distinct entities. Advanced-stage disease (UICC/AJCC III/IVA-IVC) at initial diagnosis was present in the majority of patients (64/114). Immunohistochemical staining revealed positivity for CD39 and CD73 in 48.2% and 21.1% on tumor cells (TPS ≥ 1%) as well as 46.4% and 42.9% within the immune cell infiltrate (IPS ≥ 1%), respectively. Further comparative analyses revealed immune-cold entities such adenoid cystic carcinoma (AdCC), immune-hot tumors such as adenocarcinoma, not otherwise specified (AC (NOS)) and entities with intermediate immunologic features such as acinic cell carcinoma (ACC). CONCLUSION: Current results indicate entity-specific adenosine signaling signatures. These findings suggest that the adenosine pathway plays a decisive role in tumor immunity among the major spectrum of SGCs. Targeting the adenosine pathway might pose a promising therapeutic option for selected entities.
BACKGROUND: In salivary gland carcinomas (SGC), there is only a small fraction of entities that appears to profit from immune checkpoint inhibition (ICI). Recent findings connected the activation of adenosine-signaling with a tolerogenic microenvironment. Therefore, the inhibition of adenosine pathway markers (CD39 and/or CD73) can augment ICI and/or display a novel immunotherapeutic strategy beyond ICI. Here, we assessed the immuno-histochemical expression of CD39 and CD73 across a wide spectrum of SGCs. METHODS: In total, 114 patients with SGCs consecutively diagnosed between 2001 and 2021 were assessed for clinicopathological baseline characteristics and underwent confirmatory histopathological review. Immunohistochemical expression levels of CD39 and CD73 were assessed by applying the tumor proportion score (TPS) and the immune proportional score (IPS) comparable to PD-L1 expression analysis in routine clinical practice. Additionally, findings were correlated with PD-L1 expression levels. RESULTS: The median age was 60.6 and 51.8% patients were female. The cohort covered a spectrum of eight distinct entities. Advanced-stage disease (UICC/AJCC III/IVA-IVC) at initial diagnosis was present in the majority of patients (64/114). Immunohistochemical staining revealed positivity for CD39 and CD73 in 48.2% and 21.1% on tumor cells (TPS ≥ 1%) as well as 46.4% and 42.9% within the immune cell infiltrate (IPS ≥ 1%), respectively. Further comparative analyses revealed immune-cold entities such adenoid cystic carcinoma (AdCC), immune-hot tumors such as adenocarcinoma, not otherwise specified (AC (NOS)) and entities with intermediate immunologic features such as acinic cell carcinoma (ACC). CONCLUSION: Current results indicate entity-specific adenosine signaling signatures. These findings suggest that the adenosine pathway plays a decisive role in tumor immunity among the major spectrum of SGCs. Targeting the adenosine pathway might pose a promising therapeutic option for selected entities.
Authors: Ezra E W Cohen; Denis Soulières; Christophe Le Tourneau; José Dinis; Lisa Licitra; Myung-Ju Ahn; Ainara Soria; Jean-Pascal Machiels; Nicolas Mach; Ranee Mehra; Barbara Burtness; Pingye Zhang; Jonathan Cheng; Ramona F Swaby; Kevin J Harrington Journal: Lancet Date: 2018-11-30 Impact factor: 79.321
Authors: Arjun V Balar; Daniel Castellano; Peter H O'Donnell; Petros Grivas; Jacqueline Vuky; Thomas Powles; Elizabeth R Plimack; Noah M Hahn; Ronald de Wit; Lei Pang; Mary J Savage; Rodolfo F Perini; Stephen M Keefe; Dean Bajorin; Joaquim Bellmunt Journal: Lancet Oncol Date: 2017-09-26 Impact factor: 41.316
Authors: Barbara Burtness; Kevin J Harrington; Richard Greil; Denis Soulières; Makoto Tahara; Gilberto de Castro; Amanda Psyrri; Neus Basté; Prakash Neupane; Åse Bratland; Thorsten Fuereder; Brett G M Hughes; Ricard Mesía; Nuttapong Ngamphaiboon; Tamara Rordorf; Wan Zamaniah Wan Ishak; Ruey-Long Hong; René González Mendoza; Ananya Roy; Yayan Zhang; Burak Gumuscu; Jonathan D Cheng; Fan Jin; Danny Rischin Journal: Lancet Date: 2019-11-01 Impact factor: 79.321
Authors: Siqi Chen; Derek A Wainwright; Jennifer D Wu; Yong Wan; Daniela E Matei; Yi Zhang; Bin Zhang Journal: Immunotherapy Date: 2019-06-21 Impact factor: 4.196
Authors: Roger B Cohen; Jean-Pierre Delord; Toshihiko Doi; Sarina A Piha-Paul; Stephen V Liu; Jill Gilbert; Alain P Algazi; Silvia Damian; Ruey-Long Hong; Christophe Le Tourneau; Daphne Day; Andrea Varga; Elena Elez; John Wallmark; Sanatan Saraf; Pradeep Thanigaimani; Jonathan Cheng; Bhumsuk Keam Journal: Am J Clin Oncol Date: 2018-11 Impact factor: 2.339