2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma

Background

Periampullary adenocarcinomas are a heterogenous group of tumours. Tumour morphology, i.e. intestinal type (I-type) and pancreatobiliary type (PB-type), is a more relevant prognostic factor than anatomical origin. Despite the promising effects of cancer immunotherapy, phase I and II clinical trials have this far been disappointing in pancreas cancer. The aim of this study was to map the spatial distribution of lymphocyte subsets in the tumour microenvironment of periampullary adenocarcinoma, in relation to overall survival (OS) and morphology.

Methods

Multiplexed immunohistochemistry was performed on tissue microarrays with tumours from a well characterized consecutive cohort of 175 patients with resected periampullary adenocarcinoma. A panel of immune cell markers including CD4, CD8a, FoxP3, CD20, CD45RO and pan-cytokeratin was applied.

Results

There was no difference in infiltration levels of different lymphocyte populations when taking into account both stromal and tumour compartments, however, in the latter, there were significantly higher levels of activated CD4⁺ cells (p = 0.027) in PB-type tumors while activated CD8⁺ cells (p < 0.001), CD8⁺ Tregs (p = 0.001) FoxP3⁺CD45RO^high cells (p = 0.026) and B-cells (p = 0.011) were significantly higher in I-type tumours. In the stromal compartment, FoxP3⁺CD45RO^high cells were significantly higher in I-type tumors (p = 0.004). Several immune signatures were defined, and, notably, signatures with low overall lymphocyte infiltration had a significantly worse OS. Composition of immune signatures and their impact on OS differed depending on the tissue compartment. In the stromal compartment, a signature characterized by high levels of activated CD4⁺ and CD8⁺ cells, B-cells, FoxP3⁺CD45RO^high cells and low levels of FoxP3⁺CD45RO^low cells fared significantly better than 6 of 7 defined signatures (p = 0.045, p = 0.006, p = 0.019, p < 0.001 and, p = 0.047, respectively).

Conclusions

These data demonstrate that the composition and clinical impact of immune infiltrates in periampullary adenocarcinoma differ by morphological type as well as localisation. Hence, all these factors should be considered in studies on their prognostic and predictive ability.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Lund University.

Funding

Mrs Berta Kamprad Foundation, Skåne University Hospital Research Foundation, Lund University Medical Faculty Research grants.

Disclosure

All authors have declared no conflicts of interest.