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Supplementary Figures 1 through 16 and Supplementary Tables 1 through 3 from Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation

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posted on 2023-04-03, 23:09 authored by Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P. Stabile, Lin-Feng Chen, Jill M. Siegfried, Gutian Xiao
<p>Supplementary Figure S1. Decreased survival rate of lung cancer patients who are older than 65 and with high STAT3 activation in TAMs Supplementary Figure S2. STAT3 knockout in myeloid cells in STAT3DMye mice Supplementary Figure S3. STAT3 knockout in myeloid cells in STAT3DMye mice Supplementary Figure S4. Decreased lung tumorigenesis in urethane-treated STAT3DMye mice Supplementary Figure S5. Same pathology of the lung tumors in WT and STAT3DMye mice treated with urethane Supplementary Figure S6. Different changes in the total numbers of lung macrophages, neutrophils and lymphocytes in urethane-treated STAT3DMyc mice Supplementary Figure S7. Increased M1 macrophages but decreased M2 macrophages in the lungs of urethane-treated STAT3DMye mice Supplementary Figure S8. Lung myeloid and lymphoid cell changes in STAT3DMye mice treated with urethane Supplementary Figure S9. Expression changes of chemokines in mouse lungs by urethane Supplementary Figure S10. T-cell apoptosis by MDSCs Supplementary Figure S11. Defect in T-cell apoptosis induction by STAT3 KO macrophages Supplementary Figure S12. No obvious effect on T-cell proliferation and lung recruitment by myeloid STAT3 deletion Supplementary Figure S13. Treg cell differentiation by WT macrophages but not by STAT3 KO macrophages Supplementary Figure S14. Reversal of the decreased lung tumorigenesis in urethane-treated STAT3DMye mice by CD8 deletion Supplementary Figure S15. Quantification of the iNOS and arginase staining in the Figure 7F Supplementary Figure S16. Reduced STAT3 activation in lung tumor cells in STAT3DMye mice Supplementary Table S1. Antibodies used in this study Supplementary Table S2. Clinicopathological characteristics of lung cancer patients Supplementary Table S3. Primer pairs used for real-time PCR in the study</p>

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ARTICLE ABSTRACT

One of the most fundamental and challenging questions in the cancer field is how immunity in patients with cancer is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4+ T-helper (Th1) cells and CD8+ T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8+ T cells, enhancement of cytotoxicity toward CD4+ and CD8+ T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype. The deletion of myeloid STAT3 boosted antitumor immunity and suppressed lung tumorigenesis. These findings increase our understanding of immune programming in lung tumorigenesis and provide a mechanistic basis for developing STAT3-based immunotherapy against this and other solid tumors. Cancer Immunol Res; 5(3); 257–68. ©2017 AACR.

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