American Association for Cancer Research
Browse
00085472can152770-sup-156430_1_supp_3238142_ny8bbc.pptx (3.19 MB)

Supplemental Figure 3 from STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis

Download (3.19 MB)
figure
posted on 2023-03-30, 23:43 authored by Laura M. Jones, Miranda L. Broz, Jill J. Ranger, John Ozcelik, Ryuhjin Ahn, Dongmei Zuo, Josie Ursini-Siegel, Michael T. Hallett, Matthew Krummel, William J. Muller

Supplemental Figure 3:Stat3flx/flx/MTB/MIC tumors are unable to colonize the lungs in the presence or absence of an innate immune system

Funding

Terry Fox Frontier Program Project

McGill Integrated Cancer Research Training Program Fellowship and McGill University Health Center Studentship

McGill University Canadian Research Chair in Molecular Oncology

Genentech Predoctoral Research Fellowship, the Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award, and the Achievement Reward for College Scientists Scholarship

NIH

Canadian Cancer Society

History

ARTICLE ABSTRACT

Immunosurveillance constitutes the first step of cancer immunoediting in which developing malignant lesions are eliminated by antitumorigenic immune cells. However, the mechanisms by which neoplastic cells induce an immunosuppressive state to evade the immune response are still unclear. The transcription factor STAT3 has been implicated in breast carcinogenesis and tumor immunosuppression in advanced disease, but its involvement in early disease development has not been established. Here, we genetically ablated Stat3 in the tumor epithelia of the inducible PyVmT mammary tumor model and found that Stat3-deficient mice recapitulated the three phases of immunoediting: elimination, equilibrium, and escape. Pathologic analyses revealed that Stat3-deficient mice initially formed hyperplastic and early adenoma-like lesions that later completely regressed, thereby preventing the emergence of mammary tumors in the majority of animals. Furthermore, tumor regression was correlated with massive immune infiltration into the Stat3-deficient lesions, leading to their elimination. In a minority of animals, focal, nonmetastatic Stat3-deficient mammary tumors escaped immune surveillance after a long latency or equilibrium period. Taken together, our findings suggest that tumor epithelial expression of Stat3 plays a critical role in promoting an immunosuppressive tumor microenvironment during breast tumor initiation and progression, and prompt further investigation of Stat3-inhibitory strategies that may reactivate the immunosurveillance program. Cancer Res; 76(6); 1416–28. ©2015 AACR.