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

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.

Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer

“…Guen et al [43] showed that PVRIG had the strongest eQTL association at the PILRA locus, a risk locus for AD. a recent study [44] showed that tumors highly expressing PVRIG were characterized by high levels of TILs, strong antitumor immune responses and favorable survival, in line with our results.…”

Suppressed transcript diversity and immune response in COVID-19 ICU patients: a longitudinal study

“…Interestingly, there was an overlap of only eight transcripts (ABI3, BCL11B, CD5, CR1, EST1, PVRIG, SLC25A38, and TRBC1) between the AUC comparisons at T2 and T3 (Fig 4D). The downregulation of CD5, BCL11B, and PVRIG transcripts in the low AUC group of both T2 and T3 suggest a decreased T cell activation, TCR signaling, and an increased T cell exhaustion (Fig 4E) (23,24,25,26). When the transcripts are classified by biotype, we discover that most of the transcripts are protein coding (79% DTE at T2 and 68% DTE at T3) (Fig 4F).…”