Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Investigating the association between intra-tumoral and systemic immune biomarkers and long term survival outcomes in pancreatic adenocarcinoma (#176)

Belinda Lee 1 2 3 , Ryan Hutchinson 3 , Michael Christie 3 , Samuel Banks 3 , Lewis Au 2 , Christine Semira 1 , Ben Tran 1 2 4 , Jeanne Tie 1 2 4 , Ben Thomson 2 4 , Brett Knowles 2 4 , Lara Lipton 2 4 , Sumitra Ananda 2 4 , Peter Gibbs 1 2 3
  1. Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia
  2. The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
  3. Faculty of Medicine & Health Sciences, University of Melbourne, Melbourne, VIC, Australia
  4. Peter MacCallum Cancer Centre, Parkville, VIC, Australia

Background:

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.

Aim:

To examine the relationship between intra-tumoral immune response, systemic immune response, clinicopathological features and survival in PDAC patients.

Methods:

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.

Results:

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.

Conclusion:

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.