Poster Presentation Australasian Melanoma Conference 2026

Characterising the Tumour Microenvironment in Melanoma Patients Treated with Combination Anti-TIGIT + Anti-PD-1 Immunotherapies (#409)

Tuba N Gide 1 2 3 , Alison Potter 1 4 5 , Yizhe Mao 1 2 3 , Alexander M Menzies 1 2 3 6 7 , James S Wilmott 1 2 3 , Georgina V Long 1 2 3 6 7
  1. Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
  2. Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
  3. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  4. NSW Health Pathology, Sydney, NSW, Australia
  5. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  6. Royal North Shore Hospital, Sydney, NSW, Australia
  7. Mater Hospital, Sydney, NSW, Australia

Background and Aims: T-cell immunoreceptor with Ig and ITIM domains (TIGIT), an inhibitory immune checkpoint receptor, negatively regulates immune cell activity and modulates immune responses. Early studies suggested that dual TIGIT and programmed cell death receptor-1 (PD-1) blockade could enhance anti-tumour immunity in melanoma; however, later phase II/III trials demonstrated minimal benefit over PD-1 inhibition alone. Despite this, variability in patient outcomes indicates that a subset may still benefit. This study aimed to characterise the pre-treatment tumour microenvironment to identify biomarkers associated with differential clinical outcomes following anti-TIGIT immunotherapy in metastatic melanoma.

Methods: Twenty-eight patients treated with combination anti-TIGIT + anti-PD-1 therapies were included: 15 with stage III resectable melanoma receiving neoadjuvant therapy and 13 with unresectable stage III/IV disease. TIGIT immunohistochemistry (IHC; clone BLR047F) was performed on pre-treatment formalin-fixed paraffin-embedded melanoma specimens. Multiplex immunofluorescence staining for PD-1, PD-L1, LAG-3, HLA-DR, SOX10, and CD3 was performed to further characterise the tumour microenvironment. Gene expression profiling (NanoString) was conducted on 8 advanced melanoma specimens. In the advanced cohort, patients with PFS≥6mo were categorised as responders (n=6), while non-responders had PFS<6mo (n=7). In the neoadjuvant cohort, responders achieved pCR, near-pCR or pPR (n=10), while non-responders had pNR (n=5).

Results: TIGIT IHC expression was detected in 78% of cases, more frequently in tumour-infiltrating lymphocytes (TILs) than tumour cells (73% vs 45%). Higher TIGIT expression correlated with increasing TIL grade (P=0.0005). In the advanced cohort, TIGIT IHC expression did not differ significantly between responders and non-responders (P>0.05). However, responders demonstrated significantly higher IFNγ, PD-1, and TIGIT gene expression signatures (all P=0.036). A trend toward improved PFS was observed in patients with ≥1% TIGIT+ TILs compared to <1% (P=0.053). In the neoadjuvant cohort, TIGIT IHC expression was not associated with pathological response or recurrence-free survival. Multiplex immunofluorescence analysis is underway and will further define spatial and phenotypic immune differences between groups.

Conclusion: TIGIT IHC expression was not associated with clinical outcomes in this cohort, indicating limited utility as a standalone biomarker. However, differences in gene expression signatures and tumour immune contexture suggest that broader features of immune activation may better predict response to anti-TIGIT-based therapies.