Tumor Immune Microenvironment Differences Associated With Racial Disparities in Pancreatic Cancer

J Surg Res. 2025 Mar:307:21-32. doi: 10.1016/j.jss.2025.01.005. Epub 2025 Feb 18.

Abstract

Introduction: Racial differences in antitumoral immunity have been identified in a variety of cancers and may contribute to survival disparities, but limited data exist exploring the molecular differences in pancreatic adenocarcinoma (PDAC). Using racially diverse PDAC datasets, we explored biologic differences that may drive disparities between African American (AA) and European American (EA) PDAC patients.

Methods: Genomic PDAC mutational data was analyzed for mutational differences based on race. In a separate cohort, surgical PDAC specimens were processed for both tissue microarray and multiplex gene expression analysis using NanoString.

Results: Of the 4679 patient samples in the mutational dataset, AA PDAC patients had significantly more TP53 mutations compared to the EA cohort. The tissue microarray included 12 AA and 41 EA surgically resected treatment-naive PDAC samples. NanoString analysis revealed significant differences between AA and EA groups in immunologic gene annotations (P < 0.05).

Conclusions: In the present study, we demonstrated that across racially diverse datasets, there exist molecular and microenvironmental differences between AA and EA patients that may contribute to cancer survival disparities. 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.

Keywords: African American; European American; NanoString; Pancreatic adenocarcinoma; Pancreatic cancer; Racial disparities in Cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Black or African American* / genetics
  • Black or African American* / statistics & numerical data
  • Carcinoma, Pancreatic Ductal* / ethnology
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / immunology
  • Carcinoma, Pancreatic Ductal* / mortality
  • Female
  • Health Status Disparities*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pancreatic Neoplasms* / ethnology
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / immunology
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Tissue Array Analysis
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology
  • Tumor Suppressor Protein p53 / genetics
  • White
  • White People* / genetics
  • White People* / statistics & numerical data

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53