2019
DOI: 10.1158/1055-9965.epi-18-0955
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Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry

Abstract: Background: Tumor-specific immune response is an important aspect of disease prognosis and ultimately impacts treatment decisions for innovative immunotherapies. The atypical chemokine receptor 1 (ACKR1 or DARC) gene plays a pivotal role in immune regulation and harbors several singlenucleotide variants (SNV) that are specific to sub-Saharan African ancestry. Methods: Using computational The Cancer Genome Atlas (TCGA) analysis, case-control clinical cohort Luminex assays, and CIBERSORT deconvolution, we identi… Show more

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Cited by 54 publications
(45 citation statements)
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“… 155 , 158 , 161 Other features, such as a differential mutational landscape 157 , 163 and higher frequency of DNA copy number alterations, 161 have been reported for AA/Bs compared with NHWs, in addition to the existence of differential immune and inflammatory pathways involved in tumour-specific immune responses between the two groups. 164 , 165 As stated above, obesity is associated with increased circulating levels of insulin and inflammatory cytokines, such as IL-6, IL-8 and TNF-α and CD8 + T cells and M1 macrophages, which contribute to the development of a pro-tumorigenic microenvironment and more aggressive tumour characteristics, leading to TNBC biology in AA/B women. 128 , 166 Breast cancer research that is focused on the interplay between race/ethnicity, poverty, diet, obesity and aggressive tumour biology exemplifies the richness and complexity of hypotheses that result from the use of ecosocial/multilevel theoretical frameworks.…”
Section: Disparities In Breast Cancermentioning
confidence: 99%
“… 155 , 158 , 161 Other features, such as a differential mutational landscape 157 , 163 and higher frequency of DNA copy number alterations, 161 have been reported for AA/Bs compared with NHWs, in addition to the existence of differential immune and inflammatory pathways involved in tumour-specific immune responses between the two groups. 164 , 165 As stated above, obesity is associated with increased circulating levels of insulin and inflammatory cytokines, such as IL-6, IL-8 and TNF-α and CD8 + T cells and M1 macrophages, which contribute to the development of a pro-tumorigenic microenvironment and more aggressive tumour characteristics, leading to TNBC biology in AA/B women. 128 , 166 Breast cancer research that is focused on the interplay between race/ethnicity, poverty, diet, obesity and aggressive tumour biology exemplifies the richness and complexity of hypotheses that result from the use of ecosocial/multilevel theoretical frameworks.…”
Section: Disparities In Breast Cancermentioning
confidence: 99%
“…In addition, there was a significant increase in PD-L1 and DARC expression from CRC sections treated with sequential dose of aspirin plus FOLFOX compared other treatment combinations. Moreover, overexpression of PD-L1 and the chemokine receptor, DARC, have been reported to correlates with better prognosis among cancer cases, including CRC and particularly among MMR-proficient CRC patients [ 32 , 33 , 66 ]. The cytotoxic CD8+ T-cells have been reported to be increased by the effect of aspirin via the alteration of chemokines which also contribute to decrease in myeloid-derived suppressor cells towards modulation of apoptosis [ 67 ].…”
Section: Discussionmentioning
confidence: 99%
“…The program death-1 (PD-1), a cellular protein expressed on the surface of activated immune cells such T cells, NK cells, B cells, macrophages and several subsets of dendritic cells, interacts with PD-L1 to initiate apoptosis of immune cells [ 31 ]. This cellular interaction may also be mediated by chemokine receptors such as Duffy antigen receptor for chemokines (DARC)/ atypical chemokine receptor 1 (ACKR1) towards activation of the tumor-specific immune response by chemo-attraction of leukocytes to inflammatory sites and influencing tumor growth and metastasis [ 32 , 33 ]. Microsatellite instability-high (MSI-H) CRC, a cancer characterized by the absence of one or two mismatch repair (MMR) proteins such as MSH2, PMS2, MLH1, and MSH6 have been reported to be immunogenic with robust lymphocytic infiltrate due to increased mutational signatures [ 34 ] and this may be more frequent in CRC with mucinous histology.…”
Section: Introductionmentioning
confidence: 99%
“…Atypical chemokine receptor 1 (ACKR1) plays a pivotal role in immune regulation. AA women have a higher proportion of tumors that are ACKR1 negative compared with CA women [ 59 ]. ACKR1 positive tumors differ from ACKR1 negative tumors in their immune responses.…”
Section: Racial Disparity In the Composition Of Breast Cancer Tmementioning
confidence: 99%
“…ACKR1 expression in tumors is correlated with higher pro-inflammatory chemokines, i.e., CCL2/MCP-1. ACKR1 alleles specifically expressed in AA women likely drive these correlations, which help in the overall and relapse-free survival of patients with tumors showing higher expression of ACKR1 [ 59 ]. CCL7 is more elevated in AA women with breast cancer than in CA patients.…”
Section: Racial Disparity In the Composition Of Breast Cancer Tmementioning
confidence: 99%