Abstract LB-195: Immune cell proportions and risk of pancreatic cancer using prediagnostic bloods
Authors: Michaud Dominique S. , Ruan Mengyuan , Koestler Devin , Pei Dong , Marsit Carmen , DeVivo Immaculata , Kelsey Karl 
Published: August 2019

In 2018, approximately 55,440 individuals were diagnosed with pancreatic cancer in the US, and only 8% of these individuals will survive the next five years. Given the high fatality rate of pancreatic ductal adenocarcinoma, and the silent progression of this cancer, identifying early detection biomarkers for risk stratification for screening and surveillance is critical to improve prognosis. While the immune response plays a critical role in tumor growth and survival, understanding its role in the development of cancer has been hampered by the lack of data on immune status prior to cancer diagnosis. The identification of DNA methylation markers to estimate immune cell proportions in archived bloods provides a method to examine the long-term impact of immune cell types on pancreatic cancer risk. For this study, we included pre-diagnostic bloods from 322 pancreatic cancer cases and 343 controls (matched on age, race, sex, date of blood draw) from three independent prospective cohort studies to examine associations with immune cell proportions based on validated differentially methylated regions (DMRs) of cell lineage. DNA methylation from archived buffy coat samples for the cases and controls was measured using Illumina’s Infinium MethylationEPIC array; the range of time of blood draw to cancer diagnosis in cancer patients was 6 months to 26 years. We examined associations with pancreatic cancer for the methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) and the ratio of CD4/CD8 cell types. The NLR has been linked to pancreatic cancer prognosis in several studies but has never been examined as a risk factor for incidence of pancreatic cancer (i.e., using blood drawn prior to cancer diagnosis). The CD4/CD8 ratio reflects the overall balance of T helper cells to cytotoxic T cells which is known to play a role in cancer immune surveillance in the tumor environment, and it may be associated with risk prior to diagnosis. In this nested case-control study, mdNLR was not associated the risk of pancreatic cancer (conditional OR = 1.19, 95% CI = 0.81 to 1.75, comparing top to bottom tertiles of mdNLR, additionally adjusting for smoking status). Furthermore, the association did not vary by sex or by time between blood draw and cancer diagnosis (&lt; 5 years, OR = 1.18; 5-10 years, OR = 1.22; &gt;10 years, OR =1.21). Similarly, we observed no association for the CD4/CD8 ratio and pancreatic cancer risk (OR = 0.94, 95% CI = 0.63 to 1.41) overall, or by time between blood draw and cancer diagnosis (&lt; 5 years, OR = 0.97; 5-10 years, OR = 0.62; &gt;10 years, OR =1.17). Our findings suggest that while the mdNLR may provide valuable information on prognosis after diagnosis of pancreatic cancer, a higher mdNLR in healthy individuals did not increase the risk of developing pancreatic cancer. In addition, prediagnostic CD4/CD8 ratio was not associated with pancreatic cancer risk. Further work examining additional immune cell type subfractions is currently underway.

Citation Format: Dominique S. Michaud, Mengyuan Ruan, Devin Koestler, Dong Pei, Carmen Marsit, Immaculata DeVivo, Karl Kelsey. Immune cell proportions and risk of pancreatic cancer using prediagnostic bloods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-195.