Prognostic Value of CXCR2 in Breast Cancer

Boissière, Florence; Jacot, William; Fraisse, Julien; Gourgou, Sophie; Timaxian, Colin; Lazennec, Gwendal

doi:10.3390/cancers12082076

Cited by 25 publications

(28 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because we previously demonstrated that CXCR2 stained mainly stromal cells and in particular neutrophils [ 33 ], we turned our attention to the correlations between CXCR2 and CD11b and CD66b. We observed a difference in terms of tumor infiltration for CD11b-, CD66b- and CXCR2-positive cells ( p < 0.001), with CXCR2 showing the highest infiltration (median: 1591 CXCR2+ cells/cm²; range: 0–540,653 CXCR2+ cells/cm²), followed by CD11b (median: 1305 CD11b+ cells/cm²; range: 0–205,122 CD11b+ cells/cm²) and CD66b (median: 90 CD66b+ cells/cm²; range: 0–431,006 CD66b+ cells/cm²).…”

Section: Resultsmentioning

confidence: 99%

“…CD11b, CD66b and CXCR2 expression was analyzed by immunohistochemistry of serial sections from the same TMA blocks used in our previous studies [ 7 , 36 , 37 , 38 ]. For this study, we used anti-CD11b rabbit monoclonal Ab (clone EP45 at 1/400, BioSB, Santa Barbara, CA, USA), anti-CD66b mouse monoclonal (clone 80H3 at 1/200, BioRad, Marnes-la-Coquette, France) and the recently validated anti-CXCR2 mouse monoclonal antibody (clone E-2 at 1/500, Santa Cruz Technology, Dallas, TX, USA) as previously described [ 33 ]. The rabbit monoclonal SP142 antibody (Ventana Medical Systems, Tucson, AZ, USA) was used for PD-L1 detection.…”

Section: Methodsmentioning

confidence: 99%

“…In human cancers, the function of CXCR2 has been scarcely investigated so far. We have shown recently that CXCR2 was mainly expressed by neutrophils in breast tumors and was present at higher levels in TNBC compared to luminal or Her2-positive breast cancers [ 33 ]. Interestingly, despite its high expression in high-grade tumors, CXCR2 predicted a lower risk of relapse [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Data were expressed as the number of TCRγδ-positive cells per mm 2 . CD3 + and CD8 + cell densities were assessed using the Histolab ® Image Analysis software (Microvision, Evry, France), as previously described [ 64 ]. TMA sections stained with other antibodies were analyzed independently by two trained observers, both blinded to the clinicopathological characteristics and patient outcomes at the time of scoring, as previously reported [ 35 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

Clinicopathological Correlates of γδ T Cell Infiltration in Triple-Negative Breast Cancer

Boissière

Chabab

Mollévi

et al. 2021

Cancers

Self Cite

View full text Add to dashboard Cite

The prognostic impact of the different tumor-infiltrating lymphocyte (TIL) subpopulations in solid cancers is still debated. Here, we investigated the clinicopathological correlates and prognostic impact of TILs, particularly of γδ T cells, in 162 patients with triple-negative breast cancer (TNBC). A high γδ T cell density (>6.625 γδ T cells/mm2) was associated with younger age (p = 0.008), higher tumor histological grade (p = 0.002), adjuvant chemotherapy (p = 0.010), BRCA1 promoter methylation (p = 0.010), TIL density (p < 0.001), and PD-L1 (p < 0.001) and PD-1 expression (p = 0.040). In multivariate analyses, γδ T cell infiltration (cutoff = 6.625 γδ T cells/mm2) was an independent prognostic factor (5-year relapse-free survival: 63.3% vs. 89.8%, p = 0.027; 5-year overall survival: 73.8% vs. 89.9%, p = 0.031, for low vs. high infiltration). This prognostic impact varied according to the tumor PIK3CA mutational status. High γδ T cell infiltration was associated with better survival in patients with PIK3CA wild-type tumors, but the difference was not significant in the subgroup with PIK3CA-mutated tumors. Altogether, these data suggest that high γδ T cell infiltrate is correlated with immune infiltration and might represent a candidate prognostic tool in patients with TNBC.

show abstract

“…AhR overexpression in this setting is closely associated with elevated expression of the NF-κB subunit RelB and the inflammatory markers IL-8 (CXCL1 in mouse) and COX-2 (19). Interestingly, COX-2 and chemokines such as CXCL1, CXCL5, and the chemokine receptor CXCR2 have been identified as critical genes that mediate breast cancer metastasis to lung, lymph nodes, and bone (20)(21)(22). A recent genome wide analysis of AhR and AhRR binding found a significant overlap in sequences binding both proteins, suggesting that AhRR most likely functions as a tumor suppressor by opposing AhR-driven gene expression (23).…”

Section: Introductionmentioning

confidence: 99%

Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development

et al. 2021

Self Cite

View full text Add to dashboard Cite

Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to known human carcinogens including dioxins can lead to the promotion of breast cancer. While the repressor protein of the AhR (AhRR) blocks the canonical AhR pathway, the function of AhRR in the development of breast cancer is not well-known. In the current study we examined the impact of suppressing AhR activity using its dedicated repressor protein AhRR. AhRR is a putative tumor suppressor and is silenced in several cancer types, including breast, where its loss correlates with shorter patient survival. Using the AhRR transgenic mouse, we demonstrate that AhRR overexpression opposes AhR-driven and inflammation-induced growth of mammary tumors in two different murine models of breast cancer. These include a syngeneic model using E0771 mammary tumor cells as well as the Polyoma Middle T antigen (PyMT) transgenic model. Further AhRR overexpression or knockout of AhR in human breast cancer cells enhanced apoptosis induced by chemotherapeutics and inhibited the growth of mouse mammary tumor cells. This study provides the first in vivo evidence that AhRR suppresses mammary tumor development and suggests that strategies which lead to its functional restoration and expression may have therapeutic benefit.

show abstract

Prognostic Value of CXCR2 in Breast Cancer

Cited by 25 publications

References 39 publications

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Clinicopathological Correlates of γδ T Cell Infiltration in Triple-Negative Breast Cancer

Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development

Contact Info

Product

Resources

About