PDL1, VISTA, LAG3 And CTLA4 Expression In The Laryngeal Cancer Microenvironment: Is There A Prognostic Impact Of Immune Checkpoint Molecules?
XXIII IFOS World Congress of Otorhinolaryngology – Head and Neck Surgery (IFOS 2026), İstanbul, Türkiye, 9 - 13 Eylül 2026, ss.359, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: İstanbul
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.359
- İstanbul Üniversitesi Adresli: Evet
Özet
BACKGROUND & AIM
Immune checkpoint molecules (ICMs) may influence tumor immune escape and clinical outcomes in laryngeal squamous cell carcinoma (LSCC). We evaluated the expression of programmed death ligand 1 (PDL1), V domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3), and cytotoxic T lymphocyte associated protein 4 (CTLA4) in tumor and immune compartments and investigated their associations with survival and histopathologic parameters.
MATERIAL & METHODS
In this single center retrospective cohort, surgically treated LSCC patients (2018–2022) with pathologic stage ≥3 and ≥3 years follow up after open partial or total laryngectomy ± neck dissection were included (n=101). Sixty two patients were excluded due to early stage disease, non SCC histology, or unavailable specimens. PDL1 and VISTA were scored using tumor proportion score (TPS) and combined positive score (CPS); staining intensity was recorded in tumor and immune compartments by immunohistochemistry. LAG3 and CTLA4 were assessed in the immune microenvironment by extent and intensity. Inter parameter correlations were analyzed using Spearman’s rho. Overall survival (OS) and recurrence free survival (RFS) were evaluated using Kaplan Meier and Cox regression.
RESULTS
Among 101 patients, 78 (77.2%) underwent total and 23 (22.8%) partial laryngectomy; 96 (95.0%) had lateral neck dissection. Median age was 62.3 years, 93.1% were male; overall mortality was 42.6% (disease specific 20.8%), recurrence 22.8%, median follow up 64.7 months. PDL1 TPS, PDL1 CPS, VISTA TPS, and VISTA CPS were ≥1 in 49.5%, 91.1%, 38.6%, and 99.0%; LAG3 and CTLA4 immune staining was present in 77.2% and 24.8%. PDL1 TPS correlated with VISTA immune intensity (ρ=0.205, p=0.039); VISTA immune intensity correlated with LAG3 immune extent (ρ=0.349, p<0.001) and CTLA4 immune extent (ρ=0.241, p=0.015); LAG3 immune extent correlated with CTLA4 immune extent (ρ=0.511, p<0.001). Older age (HR=1.064,p=0.003) and perineural invasion (PNI) (HR=1.911,p=0.044) predicted worse OS. For RFS, worse surgical margin status (HR=1.805,p=0.003), higher pathologic stage (HR=2.471,p=0.006), and PNI (HR=2.992,p=0.026) increased recurrence risk, whereas higher PDL1 tumor intensity (HR=0.465,p=0.015) and diffuse LAG3 immune extent (HR=0.086,p=0.021) were protective.
CONCLUSIONS
Higher PDL1 tumor intensity and diffuse LAG3 immune extent were independently associated with improved RFS. ICMs were not independently predictive of OS, whereas PNI was a consistent adverse factor for both OS and RFS. Integrated ICM profiling may aid risk stratification and warrants validation in large prospective studies to inform future immunotherapy oriented approaches in LSCC.