African American (AA) men are two to three times more likely to die from prostate cancer (PCa) than European American (EA) men. This disparity may be due in part to socioeconomic status and discrepancies in access to quality care. Studies also suggest that differences in innate immune effector cells and function in the tumor microenvironment of AA men may promote PCa aggressiveness. Increased tumor- associated macrophages are associated with poorer outcomes and a high neutrophil- to-lymphocyte ratio is significantly associated with poorer survival in men with PCa. However, the prevalence of innate immune cells, their spatial localization, and their relationship to PCa racial disparities is largely unknown. We evaluated CD66ce+ neutrophils and CD68+ (pan), CD80+ (M1), and CD163+ (M2) macrophages using RNA in situ hybridization or immunohistochemistry on formalin-fixed paraffin-embedded whole tissue sections from prostate donor tissues with no cancer (n=4) and radical prostatectomy tissues from AA and EA men with low grade (Gleason ≤ 3+4) and higher grade (Gleason ≥ 4+3) PCa (n=38). Tissue microarray (TMA) sets containing radical prostatectomy tissues (n=932) or distant metastatic tissues obtained at autopsy (n=6) were also evaluated. Immune marker expression in TMAs was quantified using TMAJ and FrIDA software. CD66ce+ neutrophils were primarily localized to blood vessels in organ donor prostate specimens as well as normal appearing, non-inflamed regions of radical prostatectomy specimens. Increased CD66ce+ neutrophils were present in inflamed regions of benign tissues from both races. In analysis of TMAs, there was significantly increased CD66ce+ neutrophils in tissues from EA men compared to AA men (p < 0.0001). There was also increased CD66ce expression in cancer compared to benign tissue spots (p <0.01), in low grade compared to higher grade cancer (p < 0.0001), in cancer with PTEN loss versus intact PTEN (p < 0.0001), and in ERG positive versus ERG negative cancer (p = 0.0011).
There was no association between CD66ce+ neutrophils and risk of metastasis or biochemical recurrence. CD68+ and CD163+ macrophages were abundant in organ donor specimens, while CD80 expression was minimal. Similar expression patterns were observed in benign regions of radical prostatectomy specimens. In analysis of TMAs, CD68, CD80 and CD163 were significantly increased in cancer compared to benign tissues (p < 0.0001). CD163 expression was comparable between races, while CD80 expression was significantly higher in benign tissues from AA men compared to EA men (p = 0.0004). CD68, CD80 and CD163 expression were all significantly increased in benign spots from ERG positive versus ERG negative cases. In conclusion, there is increased infiltration of innate immune cells in the prostate tumor microenvironment of both AA and EA men, however the composition of innate immune cell infiltration varies between races. Our future studies aim to determine the influence of innate immune effector cells on PCa aggressiveness and outcomes.
Citation Format: Janielle P. Maynard, Jiayun Lu, Igor Vidal, Corinne E. Joshu, Angelo M. De Marzo, Karen S. Sfanos. Localization of macrophages and neutrophils in the prostate tumor microenvironment and their association with prostate cancer racial disparities [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-226.