eptor Tyrosine Kinase Signaling Favors a Protumorigenic te in Breast Cancer Cells by Inhibiting the Adaptive

ownloade g transgenic mouse models of breast cancer that ablate Src homology and collagen A (ShcA) expression ogene-coupled ShcA signaling, we previously showed that this adaptor is critical for mammary tumor and progression. We now provide the first evidence that ShcA regulates mammary tumorigenesis, in hrough its ability to regulate the adaptive immune response. Inactivation of ShcA signaling within tumor esults in extensive CD4 T-cell infiltration and induction of a humoral immune response in mammary s. This is associated with a robust CTL response in preneoplastic lesions that are deficient in ShcA ng. Moreover, mammary tumor progression of ShcA-deficient hyperplasias is accelerated in a T cell– nt background. We also uncover a clinically relevant correlation between high ShcA expression and TL infiltration in human breast cancers. Finally, we define a novel ShcA-regulated immune signature nctions as an independent prognostic marker of survival in human epidermal growth factor receptor that fu 2 and basal breast cancers. We reveal a novel role for tumor cell–derived ShcA in the establishment and maintenance of an immunosuppressive state. Cancer Res; 70(20); 7776–87. ©2010 AACR.

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