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Figure 8 | BMC Cancer

Figure 8

From: Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules

Figure 8

Proposed model of how immune response pathways affect clinical outcome in ER- breast cancer. Figure adapted from [26]. Hypothetical model in which the balance of cytokines in the breast tumour microenvironment determines the relative strength of Th1 and Th2 differentiation. Stronger activation of a Th1 immune response leads to increased production of IL2 and IFNG which mediate formation of M1 macrophages and cytotoxic killer cells, which is tumour inhibitory [26]. Correspondingly we observe that genes that are upregulated in these pathways are associated with good prognosis (DMFS) in ER- breast cancer (significant associations shown in green). Conversely, stronger activation of a Th2 immune response leads to production of IL13 and TGFB cytokines through an M2 macrophage polarization program. The cytokine TGFB is known to suppress the tumour inhibitory role of Th1 [26]. Correspondingly, we observe that genes that are upregulated in these pathways confer poor prognosis (DMFS) (significant associations shown in blue). Genes implicated in the Th1 and Th2 pathways were generally anticorrelated, indicative of an unbalanced differentiation program. It follows from this model that simultaneous high Th1 (IL2, IL12, IFNG) and low TGFB would confer better prognosis than either high Th1 or low TGFB alone, in agreement with our observations.

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