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Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
PVRIG Expression Is an Independent Prognostic Factor and a New Potential Target for Immunotherapy in Hepatocellular
David Jeremie Birnbaum1,2, Maelle Picard1, Quentin Da Costa1
1Predictive 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.
Abstract:
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.
Insights
Hepatocellular carcinoma (HCC) research identifies PVRIG as a promising target for immunotherapy. Targeting the TIGIT/DNAM-1 axis may improve treatment outcomes for HCC patients with high PVRIG expression.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Hepatocellular carcinoma (HCC) is a significant cause of cancer-related mortality, necessitating novel therapeutic strategies.
- Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has shown efficacy in various solid tumors.
- The TIGIT/DNAM-1 axis presents a potential target for developing new immunotherapeutic agents for HCC.
Purpose of the Study:
- To investigate the TIGIT/DNAM-1 axis as a therapeutic target in hepatocellular carcinoma.
- To analyze the expression patterns and prognostic significance of TIGIT/DNAM-1 axis members in HCC.
- To identify clinical and biological characteristics associated with PVRIG expression in HCC.
Main Methods:
- Construction of a comprehensive transcriptomic database from 683 HCC and 319 normal liver tissue samples.
- Interrogation of the database for transcriptomic expression of TIGIT/DNAM-1 axis members.
- Prognostic value assessment and analysis of clinical features and biological pathways linked to PVRIG expression.
Main Results:
- PVRIG expression was significantly higher in HCC tumors compared to normal liver tissue.
- PVRIG was the sole TIGIT/DNAM-1 axis member demonstrating independent prognostic value for improved survival in HCC.
- PVRIG-high HCC tumors exhibited increased lymphocytic infiltration and enrichment of pathways related to tertiary lymphoid structures and anti-tumor immunity.
Conclusions:
- PVRIG expression in HCC is associated with favorable prognostic indicators and enhanced anti-tumor immune responses.
- Patients with PVRIG-high HCC may benefit from immunotherapies targeting the TIGIT/DNAM-1 axis.
- Further functional and clinical studies are warranted to validate PVRIG as a therapeutic target in HCC.
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