Longitudinal tissue-based evaluation of TIGIT expression in patients with pancreatic cancer: Effect of expression with advancing clinical stages and across racial groups.

Abstract

e16314 Background: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially to a lack of early detection biomarkers and resistance to standard therapeutic options. TIGIT, an immune checkpoint receptor, is a marker of T-cell exhaustion and plays a key role in the inhibition of anti-tumor immune responses. TIGIT inhibitors are being explored in clinical trials in PDAC. Here we evaluate TIGIT expression in a cohort of PDAC patients and correlate level and intensity of expression with clinical parameters. We also examine changes in expression as the disease progresses from primary to metastatic disease. Methods: We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA on 82 formalin-fixed paraffin-embedded (FFPE) tissue samples. The cohort of tissue samples included 9 biopsies, 67 primary resections and 6 metastatic lesions. We evaluated the total TIGIT expression (%) as well as the intensity of TIGIT expression (% of cells with 3+ punctae, signifying putative immune cells), and compared these values between samples. Utilizing linear regression for continuous outcomes and logistic regression for binary outcomes, we tested for associations between TIGIT expression and clinical covariates. Results: Staining analysis showed that TIGIT expression did not differ significantly between racial groups. The mean percentage of TIGIT positive cells was 64.0%. High expression of TIGIT was associated with more advanced clinical stage (p < 0.05). Evaluation of three longitudinal samples from the same patient revealed decreased TIGIT expression from the initial biopsy (41.6%) to resection (33.4%) and metastasis (2.8%). In these specimens, 3+ TIGIT expression also declined (2.1%, 1.2% and 0.02%, respectively). Conclusions: Anti-TIGIT therapy has potential to reverse immune suppression and, with other therapeutic modalities, may provide survival benefit. Here we demonstrate that increased TIGIT expression correlates with more advanced stage at diagnosis and also present data demonstrating that overall TIGIT expression, as detected by RNAscope ISH, may decrease as PDAC progresses to metastasis. As such, anti-TIGIT therapy may have important implications for evading an important mechanism of cancer progression.