PVRIG Expression Is an Independent Prognostic Factor and a New Potential Target for Immunotherapy in Hepatocellular Carcinoma.

Autor: Birnbaum DJ; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France.; General and Visceral Surgery Department, North's Hospital, 13015 Marseilles, France., Picard M; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France., Da Costa Q; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France., Delayre T; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France.; General and Visceral Surgery Department, North's Hospital, 13015 Marseilles, France., Finetti P; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France., Cabaud O; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France., Agavnian E; IPC/CRCM Experimental Pathology (ICEP), CRCM, Paoli-Calmettes Institute, 13009 Marseilles, France., De Rauglaudre B; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France.; Department of Digestive Oncology and Gastro-Enterology, Timone Hospital, AP-HM, 13005 Marseille, France., Denicolaï E; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France., Bertucci F; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France.; Department of Medical Oncology, Paoli-Calmettes Institute, 13009 Marseilles, France., Mamessier E; Predictive Oncology Laboratory, Labeled Team Ligue Nationale Contre Le Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Paoli-Calmettes Institute (IPC), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University, 13009 Marseilles, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jan 10; Vol. 15 (2). Date of Electronic Publication: 2023 Jan 10.
DOI: 10.3390/cancers15020447
Abstrakt: Hepatocellular carcinoma (HCC) is a frequent and deadly cancer in need of new treatments. Immunotherapy has shown promising results in several solid tumors. The TIGIT/DNAM-1 axis gathers targets for new immune checkpoint inhibitors (ICIs). Here, we aimed at highlighting the potential of this axis as a new therapeutic option for HCC. For this, we built a large transcriptomic database of 683 HCC samples, clinically annotated, and 319 normal liver tissues. We interrogated this database for the transcriptomic expression of each member of the TIGIT/DNAM-1 axis and tested their prognostic value for survival. We then focused on the most discriminant one for these criteria, i.e., PVRIG , and analyzed the clinical characteristics, the disease-free and overall survivals, and biological pathways associated with PVRIG High tumors. Among all members of the TIGIT/DNAM-1 axis, PVRIG expression was higher in tumors than in normal liver, was heterogeneous across tumors, and was the only member with independent prognostic value for better survival. PVRIG High tumors were characterized by a higher lymphocytic infiltrate and enriched for signatures associated with tertiary lymphoid structures and better anti-tumor immune response. These results suggest that patients with PVRIG High tumors might be good candidates for immune therapy involving ICIs, notably ICIs targeting the TIGIT/DNAM-1 axis. Further functional and clinical validation is urgently required.
Databáze: MEDLINE
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