Abstract C120: Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities
Authors: Jarrett Jelani , Lee Jae W , Dbouk Ali , Manoharan Vahinipriya , Rains Kennedy , Mason Terri , Levinson Kimberly , Wood Laura D , Goggins Michael G , Maynard Janielle P 
Published: September 2024

Black persons have the highest mortality rates of both cervical cancer (CC) and pancreatic ductal adenocarcinoma (PDAC) in the United States. Differences in access to quality healthcare and socioeconomic status contribute to these cancer health disparities as well as ancestry and biology. In other cancer types, differences in the inflammatory tumor landscape across races and ancestral populations have been reported. However, the inflammatory tumor microenvironment (TME) as it relates to CC and PDAC health disparities is not well defined. Black patients are often underrepresented in PDAC studies. Meanwhile, CC health disparities studies primarily investigate socioeconomic status, screening, and vaccination rates. Therefore, we aim to characterize the inflammatory TME in these two cancer types with the long-term goal of informing prevention, prognostic, and therapeutic strategies. Clinicopathological characteristics were compared between Black (n = 144) and White (n = 198) patients with CC who received care at Johns Hopkins Medicine between 1995 and 2019. Surgically resected formalin-fixed paraffin embedded (FFPE) CC tissue samples were obtained from Non-Hispanic Black (n = 10), Non-Hispanic White (n = 10), Hispanic Black (n = 5), and Hispanic White (n = 5) women matched on grade, age, and subtype. Tissue microarrays (TMAs) were constructed using archival surgically resected FFPE PDAC tissues from Black (n = 45) and White (n = 45) patients, matched on sex, age, stage, and time of surgery. Multiplexing immunohistochemistry (mIHC) was used to assess markers for i) T cells (CD3, CD8, CD4, FoxP3), M2 macrophages (CD163), mast cells (Tryptase), and fibroblasts (FAP) in PDAC tissues and ii) B cells (CD79A), T cells (CD3, CD8, CD4, FoxP3), plasma cells (CD138/syndecan-1), programmed death-ligand 1 protein (PD-L1), macrophages (CD68, CD163), natural killer cells (NKP46/CD56/CD16), neutrophils (CD66ce), and mast cells (Tryptase) in CC tissues. HALO Image Analysis Platform (version 3.6.4134.137; Indica Labs) was used to quantify marker expression. GraphPad Prism Software (version 10.0.03), was used for graphing and statistical analysis. Squamous cell CC was the most frequent histological subtype in both Black (68%) and White (44%) women. Progression through treatment was more common among Black women (24%) compared to White women (7%). CD163+ M2 macrophages were significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0435), and in tumors from Black women compared to White women (p = 0.0067). FAP+ fibroblasts were also significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0001) and in tumors from Black women compared to White women (p = 0.0013). CD8+ cytotoxic T cells and FoxP3+ regulatory T cells were comparable between races. We observed differences in macrophage and fibroblast distribution between races supporting the effort for future studies that examine the significance of characterizing the TME to address cancer health disparities.

Citation Format: Jelani Jarrett, Jae W Lee, Ali Dbouk, Vahinipriya Manoharan, Kennedy Rains, Terri Mason, Kimberly Levinson, Laura D Wood, Michael G Goggins, Janielle P Maynard. Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C120.