45: Differential Immune Signatures are Associated with Racial Disparities in Pancreatic Cancer

Saturday, March 25, 2023

9:46 AM – 9:56 AM

Location: Ballroom A

Abstract Presenter(s)

Zachary Gao, MD

Research Resident
Baylor College of Medicine
Houston, Texas, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

Zachary Gao, MD

Research Resident
Baylor College of Medicine
Houston, Texas, United States

Disclosure(s): No financial relationships to disclose

Author(s)

ZS

Zequn Sun, PhD

Biostatistician
Northwestern University, United States

Disclosure information not submitted.
DE

Derek Erstad, MD

Physician
Baylor College of Medicine, United States

Disclosure information not submitted.
DC

Dongjun Chung, PhD

Biostatistician
Ohio State University, United States

Disclosure information not submitted.
WF

William Fisher, MD

Physician
Baylor College of Medicine, United States

Disclosure information not submitted.
GV

George Van Buren, MD

Physician
Baylor College of Medicine, United States

Disclosure information not submitted.
DL

David Lewin, MD

Physician
Medical University of South Carolina, United States

Disclosure information not submitted.
E. Ramsay Camp, MD, MSCR

Chief, Division of Surgical Oncology Olga Keith Wiess Chair of Surgery Michael E. DeBakey Department of Surgery
Baylor College of Medicine
Houston, TX, United States

Disclosure information not submitted.

Disclosure(s):

Zachary Gao, MD: No financial relationships to disclose

Introduction: Racial differences in anti-tumoral immunity have been implicated in various cancer disparities. The lack of racial diversity in publicly available pancreatic adenocarcinoma (PDAC) genomic datasets limits the ability to explore possible racial differences underlying PDAC. Using a racially diverse PDAC tissue bank, we hypothesized that African American (AA) PDAC tumors would demonstrate unfavorable immune parameters compared to European American (EA) PDAC tumors.

Methods: Surgical PDAC specimens from AA and EA patients were processed for both tissue microarray (TMA) and multiplex gene expression analysis using NanoString. TMAs were reviewed by a pathologist blinded to patient data. NanoString analysis was performed using the NanoStringDiff package on R. Gene set enrichment analyses based on Fisher’s exact test were also implemented using the nCounter Human Immunology V2 Panel. Differential gene expression was determined using race as the variable of interest, while adjusting for age, sex, and grade with a nominal false discovery rate (FDR) of 0.05. Genes of interest were further characterized using the TCGA PDAC and GTEx datasets.

Results: 11 AA and 29 EA PDAC samples were processed after confirming histopathologic diagnosis and excluding neoadjuvant treatment. There was no significant difference seen in lymphoid infiltration, neutrophil infiltration, tertiary lymphoid structures, or tumor budding between groups. NanoString analysis revealed significant differences between AA and EA groups in gene annotations for the adaptive immune system, chemokine signaling, cytokine signaling, NF-kB signaling, and T-cell receptor signaling (p < 0.05).
Adjusting for FDR, IL11 and PPARG genes had significantly increased expression in AA compared to EA samples (p < 0.05). IL11 is an interleukin affecting inflammation, motility, and invasion in multiple cancers, and PPARG is a member of the peroxisome proliferator activated receptor family mediating adipocyte differentiation. Based on TCGA PDAC and GTEx data, both IL11 and PPARG are significantly overexpressed in PDAC tissue compared to normal pancreatic tissue (p < 0.05) and are associated with worse survival in PDAC patients based on Kaplan-Meier quartile estimates (p < 0.05).

Conclusions: Our evidence suggests differences in key immune pathways exist between AA and EA PDAC patient populations and highlights a need for more racially diverse PDAC datasets. Defining molecular differences underlying PDAC racial disparities is an essential step in advancing care and improving outcomes for AA patients that suffer worse survival across cancer types.

Learning Objectives:

appreciate the contribution of the immune system in tumorigenesis.
understand the need for targeted therapy for pancreatic cancer.
understand the need for racial diversity in genomic datasets.