E220: TIGIT expression increases with advancing clinical stages of resected pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal 12% 5-year survival rate due to a lack of early detection biomarkers and resistance to standard therapeutic options (surgery, chemotherapy, radiation). 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 pancreatic cancer. We evaluated TIGIT expression to determine if it correlates with increasing clinical stage.

Methods:

We analyzed publicly available single-cell RNA sequencing data (scRNAseq) to survey TIGIT expression in 52 primary PDAC tumors. We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA (combined with a nuclear counterstain) on 48 primary (surgical resection) and 4 metastatic (liver core biopsies) formalin-fixed paraffin-embedded (FFPE) tissue sections from patients with histologically confirmed PDAC. The presence of TIGIT probe within the cytoplasm of each cell was determined and quantified, with percent positive cell values exported for statistical analysis in R. De-identified clinical metadata was obtained from REDCap, a HIPAA-compliant database. We tested for associations between TIGIT expression and clinical covariates, using linear regression for continuous outcomes, and logistic regression for binary outcomes.

Results:

ScRNAseq revealed that TIGIT mRNA is enriched in, but not exclusive to the T/NK cellular compartments in PDAC. Staining analysis showed that TIGIT expression did not differ significantly between racial groups (comparing non-Black African American to Black African American). The mean percentage of TIGIT positive cells was 63.3%. High expression of TIGIT was associated with clinical stage, where an increase in stage was associated with increasing %TIGIT (p < 0.001).

Conclusions:

The TIGIT biomarker assay can be conducted at time of diagnosis, time of surgical resection, and time of metastatic biopsy. If patients’ samples contain high levels of TIGIT expression, these patients may be candidates for anti-TIGIT drug therapy. Considering that TIGIT expression correlates with advancing clinical stage, patients with more advanced staging at diagnosis (stage IIB, III, IV) especially may benefit from anti-TIGIT therapy.