Racial differences in CD8+ T cell infiltration in breast tumors from Black and White women

Abstract

Background: African American/Black women with breast cancer have poorer survival than White women, and this disparity persists even after adjusting for non-biological factors. Differences in tumor immune biology have been reported between Black and White women, and the tumor immune milieu could potentially drive racial differences in breast cancer etiology and outcome. Methods: We examined the association of CD8 + cytotoxic T cells with clinical-pathological variables in the Women's Circle of Health Study (WCHS) population of predominantly Black breast cancer patients. We evaluated 688 invasive breast tumor samples (550 Black, 138 White) using immunohistochemical staining of tissue microarray slides. CD8 + T cells were scored for each patient tumor sample with digital image analysis. Results: Black women had a significantly higher percentage of high-grade, estrogen receptor (ER)-negative, and triple-negative tumors than White women and significantly higher CD8 + T cell density (median 87.6/mm 2 vs. 53.1/ mm 2 ; p < 0.001). Within the overall population and in the population of Black women only, CD8 + T cell density was significantly higher in younger patients and patients with high-grade and ER/PR-negative tumors. No significant associations were observed between CD8 + T cell density and overall survival or breast cancer-specific survival in the overall population, or when Black patients were analyzed as a separate group. However, when stratified by subtype, Black women with triple-negative breast cancer and high CD8 + T cell density showed a trend towards better overall survival in comparison with patients with low CD8 + T cell density (HR = 0.51; 95% CI 0.25-1.04). Conclusions: Our data raise the possibility that distinct mechanisms of immune cell action may occur in different racial groups.

Concomitant activation of GLI1 and Notch1 contributes to racial disparity of human triple negative breast cancer progression

“…AA women exhibit higher tumor-infiltrating CD8 + T cell density compared to white women indicating a potential involvement of immune landscape in racial disparity. Although no clear association is observed between CD8 + T cell density and overall survival, higher CD8 + T cell density in AA-TNBC associate with better overall survival which is paradoxical ( Abdou et al, 2020 ). Interestingly, exosome analysis shows higher expression of exosomal-Annexin 2 (exo-AnxA2) in the sera of AA women with TNBC indicating its potential role in angiogenesis and tumor promotion ( Chaudhary et al, 2020 ).…”

Race as a Contributor to Stromal Modulation of Tumor Progression

“…Breast cancer TILs include a large portion of T cells (CD8+ and CD4+ T cells), and smaller portions of B cells and NK cells [ 83 ]. CD8+ T cell density is higher in AA breast tumors compared to EA women and is associated with improved clinical outcomes in the AA population [ 84 ]. While increased CD8+ T cell density is linked to an overall increase in breast cancer patient survival rates, CD8+ T cell exhaustion contributes to a poor prognosis due to decreased effector cytokine production.…”

Molecular and Cellular Factors Associated with Racial Disparity in Breast Cancer

“…TILs are predominantly comprised of B cells, T cells, and NK cells, playing a crucial role in antitumor immune response [ 26 ]. AA women with the Basal/TNBC subtypes are reported to show more regulatory T cells (Tregs), while there are more CD8 + lymphocytes only in the luminal subtypes of breast cancer in AA women [ 27 , 28 ]. A higher number CD8 + T cells is indicative of a favorable response to neoadjuvant therapy in various molecular subtypes of breast cancer [ 25 , 29 , 30 ].…”

“…A higher number CD8 + T cells is indicative of a favorable response to neoadjuvant therapy in various molecular subtypes of breast cancer [ 25 , 29 , 30 ]. Furthermore, immunohistochemical staining of CD8 + T cells revealed that a higher percentage of CD8 + T cells are recruited in the tumor of AA breast cancer patients compared to CA women with breast cancer, which is suggestive of the mounting of strong immune response [ 27 ]. Other groups have also identified differential TIL in TNBC between AA and CA [ 23 , 24 ].…”