Role and clinical significance of VISTA (PD-1H) and PVR (CD155) expression in non-small cell lung carcinoma: a systematic review

Background: Immune checkpoint blockade has improved outcomes in non-small cell lung carcinoma (NSCLC), yet primary and acquired resistance remain common. VISTA (PD-1H) and CD155 (poliovirus receptor, PVR) are emerging immune-regulatory pathways that may contribute to immune escape and represent potential therapeutic targets. Thus, this systematic review aimed to evaluate the expression patterns, molecular functions, and clinical significance of CD155 (PVR) and VISTA (PD-1H) in NSCLC.

Methods: We performed a systematic review of studies assessing the expression, function, and clinical relevance of VISTA and/or CD155 in NSCLC. PubMed, Scopus, Embase, and Web of Science were searched through September 2025. Original human, in vivo, and in vitro studies were eligible. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS; human studies) and SYRCLE’s tool (animal studies). The protocol was registered in PROSPERO.

Results: Fifty-one studies met the inclusion criteria (22 VISTA; 29 CD155). VISTA was predominantly reported in stromal and immune-cell compartments and linked to immune-regulatory functions, but available evidence did not support a consistent association with survival. CD155 was mainly expressed on tumour cells, associated with an immunosuppressive microenvironment, and more consistently related to adverse prognosis in selected cohorts, particularly when co-expressed with programmed death-ligand 1 (PD-L1).

Conclusions: Both pathways appear involved in immune modulation in NSCLC. Evidence for VISTA as a prognostic biomarker remains inconclusive, whereas CD155 shows a more reproducible association with unfavourable outcomes, supporting its further evaluation as a prognostic marker and therapeutic target.