Abstract 2876
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+CD45ROhigh cells (p = 0.026) and B-cells (p = 0.011) were significantly higher in I-type tumours. In the stromal compartment, FoxP3+CD45ROhigh 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+CD45ROhigh cells and low levels of FoxP3+CD45ROlow 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.
Resources from the same session
5203 - Novel fusion genes identified from matched primary and recurred breast cancers by RNA-sequencing
Presenter: Soojeong Choi
Session: Poster Display session 2
Resources:
Abstract
5873 - Association between PIK3CA mutation status and development of brain metastases in HR+/HER2- metastatic breast cancer
Presenter: Donna Fitzgerald
Session: Poster Display session 2
Resources:
Abstract
3588 - The role of AXL as mechanism of resistance to trastuzumab and a prognostic factor in breast cancer HER2 positive: a translational approach.
Presenter: Anna Adam-Artigues
Session: Poster Display session 2
Resources:
Abstract
5640 - Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment
Presenter: Marija Balic
Session: Poster Display session 2
Resources:
Abstract
2616 - Clinical application of mutational analysis in breast cancer patients: the relevance of PIK3CA analysis for precision medicine.
Presenter: Juan Miguel Cejalvo
Session: Poster Display session 2
Resources:
Abstract
3870 - A retrospective gene expression analysis of surgically-removed Breast Cancer Brain Metastasis (BCBM)
Presenter: Meritxell Mallafré-Larrosa
Session: Poster Display session 2
Resources:
Abstract
1240 - Endocrine therapy alone versus targeted combination strategy as first line treatment in elderly patients with hormone receptor-positive advanced breast cancer: meta-analysis of Phase II and III randomized clinical trials
Presenter: Claudia Omarini
Session: Poster Display session 2
Resources:
Abstract
5535 - Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): management and time course of key adverse events of special interest (AESIs) in SOLAR-1
Presenter: Hope Rugo
Session: Poster Display session 2
Resources:
Abstract
3093 - Changes in Hormone-Receptor status in Luminal breast cancers between primary tumor and metastases: results of the observational cohort GIM-13 AMBRA Study
Presenter: Marina Cazzaniga
Session: Poster Display session 2
Resources:
Abstract
1378 - MONARCH 3: Updated time to chemotherapy and disease progression following abemaciclib plus aromatase inhibitor (AI) in HR+, HER2- advanced breast cancer (ABC)
Presenter: Miguel Martín
Session: Poster Display session 2
Resources:
Abstract