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. 2018 Apr;11(2):311-329.
doi: 10.1016/j.tranon.2018.01.011. Epub 2018 Feb 4.

A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer

Zhixian Liu  1 , Mengyuan Li  2 , Zehang Jiang  1 , Xiaosheng Wang  3
Affiliations

A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer

Zhixian Liu et al. Transl Oncol. 2018 Apr.

Abstract

Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. We found that almost all analyzed immune activities and pathways had significantly higher enrichment levels in TNBC than non-TNBC. Elevated enrichment of these immune activities and pathways was likely to be associated with better survival prognosis in TNBC. This study demonstrated that TNBC likely exhibits the strongest immunogenicity among BC subtypes, and thus warrants the immunotherapeutic option for TNBC.

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Figures

Figure 1
Figure 1
Comparison of expression levels of immune cell types, functional markers, and HLA genes between TNBC and non-TNBC. (A) Heat-map for expression levels of immune cell types and function genes in TNBC and non-TNBC. (B) Comparison of expression levels of the HLA gene-set between TNBC and non-TNBC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 2
Figure 2
Comparison of expression levels of TILs, immune cell infiltrate, Treg, and immune checkpoint genes between TNBC and non-TNBC. (A) Heat-map for expression levels of TILs genes in TNBC and non-TNBC. TILs: tumor-infiltrating lymphocytes. (B) Comparison of expression levels of immune cell subpopulation genes between TNBC and non-TNBC in METABRIC. *: P < 0.05; **: P < 0.01; ***: P < 0.001, and it applies to all the following box charts. C. Heat-map for expression levels of Treg and immune checkpoint genes in TNBC and non-TNBC. D. Comparison of expression levels of important immune checkpoint genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 2
Figure 2
Comparison of expression levels of TILs, immune cell infiltrate, Treg, and immune checkpoint genes between TNBC and non-TNBC. (A) Heat-map for expression levels of TILs genes in TNBC and non-TNBC. TILs: tumor-infiltrating lymphocytes. (B) Comparison of expression levels of immune cell subpopulation genes between TNBC and non-TNBC in METABRIC. *: P < 0.05; **: P < 0.01; ***: P < 0.001, and it applies to all the following box charts. C. Heat-map for expression levels of Treg and immune checkpoint genes in TNBC and non-TNBC. D. Comparison of expression levels of important immune checkpoint genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 2
Figure 2
Comparison of expression levels of TILs, immune cell infiltrate, Treg, and immune checkpoint genes between TNBC and non-TNBC. (A) Heat-map for expression levels of TILs genes in TNBC and non-TNBC. TILs: tumor-infiltrating lymphocytes. (B) Comparison of expression levels of immune cell subpopulation genes between TNBC and non-TNBC in METABRIC. *: P < 0.05; **: P < 0.01; ***: P < 0.001, and it applies to all the following box charts. C. Heat-map for expression levels of Treg and immune checkpoint genes in TNBC and non-TNBC. D. Comparison of expression levels of important immune checkpoint genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 2
Figure 2
Comparison of expression levels of TILs, immune cell infiltrate, Treg, and immune checkpoint genes between TNBC and non-TNBC. (A) Heat-map for expression levels of TILs genes in TNBC and non-TNBC. TILs: tumor-infiltrating lymphocytes. (B) Comparison of expression levels of immune cell subpopulation genes between TNBC and non-TNBC in METABRIC. *: P < 0.05; **: P < 0.01; ***: P < 0.001, and it applies to all the following box charts. C. Heat-map for expression levels of Treg and immune checkpoint genes in TNBC and non-TNBC. D. Comparison of expression levels of important immune checkpoint genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 3
Figure 3
Comparison of expression levels of metastasis-promoting, metastasis-inhibiting, inflammation-promoting, and parainflammation genes between TNBC and non-TNBC. (A) Comparison of expression levels of the metastasis-promoting and metastasis-inhibiting gene-sets between TNBC and non-TNBC. (B) Heat-map for expression levels of inflammation-promoting genes and parainflammation genes in TNBC and non-TNBC. (C) Comparison of expression levels of important inflammation-promoting genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 3
Figure 3
Comparison of expression levels of metastasis-promoting, metastasis-inhibiting, inflammation-promoting, and parainflammation genes between TNBC and non-TNBC. (A) Comparison of expression levels of the metastasis-promoting and metastasis-inhibiting gene-sets between TNBC and non-TNBC. (B) Heat-map for expression levels of inflammation-promoting genes and parainflammation genes in TNBC and non-TNBC. (C) Comparison of expression levels of important inflammation-promoting genes between TNBC and non-TNBC in METABRIC. Red color indicates higher gene expression levels, and blue color indicates lower gene expression levels.
Figure 4
Figure 4
Correlation between immune gene expression and OS prognosis in TNBC. A. Kaplan-Meier survival curves show that elevated expression of most of the immune gene-sets is associated with better OS prognosis in TNBC (log-rank test, unadjusted P-value < 0.05). B. Kaplan-Meier survival curves show that elevated expression of a number of immune genes is associated with better OS prognosis in TNBC (log-rank test, unadjusted P-value < 0.05). OS: overall survival.
Figure 5
Figure 5
Correlation between immunogenic activity and the differential expression of genes or signaling pathways between TNBC and non-TNBC. A. Correlations of immunogenic activity and expression of ESR1 and ERBB2. B. Correlations of immunogenic activity and pathway activity.
Figure 6
Figure 6
Comparison of the levels of immune cell infiltration in the tumor microenvironment between TNBC and non-TNBC. (A) TNBC shows significantly higher degree of immune cell infiltration than non-TNBC based on ESTIMATE evaluation. (B) TNBC has significantly different leukocyte cell subset infiltrates from non-TNBC based on CIBERSORT evaluation.
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