Despite immunotherapy advances, responses to date in pancreatic adenocarcinomas (PDAC) have been disappointing. An improved understanding of the systemic and intra-tumoral immune response, tumour microenvironment and its interplay in PDAC will inform immune-based approaches to PDAC.
To examine the relationship between intra-tumoral immune response, systemic immune response, clinicopathological features and survival in PDAC patients.
The international PURPLE pancreatic cancer translational registry has prospectively collected clinical data on consecutive PDAC patients. This database was interrogated to identify PDAC patients from a single centre who had undergone a tumour biopsy or primary resection. Available tissue specimens from 29 patients were scored by immunohistochemistry for the presence of PD-L1, PD-L2, cytotoxic T lymphocyte associated protein-4 (CTLA-4), indoleamine 2,3-ioxygenase (IDO) and for macrophage (M2/M1) ratio. These results were correlated against the patients’ systemic neutrophil/lymphocyte ratio (NLR), clinicopathologic features and survival outcomes.
Of 29 specimens, 51.7% (15/29) were positive for PD-L1. Only 1 of 29 was positive for PDL2. Tumour cell CTLA-4 overexpression was seen in 22 specimens (75.9%); whilst IDO overexpression was identified in 24.1% (7/29). In 12 examined specimens, 83.3% (10/12) had a high M2/M1 macrophage ratio and the remaining 2 had a low M2/M1 ratio. A trend towards poorer overall survival (OS) was seen in cases with CTLA4 tumour cell over-expression and an elevated systemic NLR >5 (p=0.09, HR 3.79, 95% CI 0.85-28.30). The presence of IDO tumour cell staining was significantly associated with a worse overall survival (p=0.01, HR=3.54, 95% CI: 1.75-36.07) with a median survival of 11.9 vs 21.7months in the IDO positive vs negative groups.
Over expression of CTLA-4 and IDO in PDAC tumours appears to correlate with poorer OS, with a trend towards a deleterious synergistic relationship between intra-tumoural immune suppression and systemic inflammation. Further analysis and expansion of the cohort is underway.