Myeloid STAT3 promotes lung tumorigenesis by transforming tumor immunosurveillance into tumor-promoting inflammation

Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P. Stabile, Lin Feng Chen, Jill M. Siegfried, Gutian Xiao

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 tumorpromoting 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.

Original languageEnglish (US)
Pages (from-to)257-268
Number of pages12
JournalCancer Immunology Research
Issue number3
StatePublished - Mar 2017

Bibliographical note

Funding Information:
This study was financially supported in part by the NIH/NCI grants R01 CA172090, R21 CA175252, R21 CA189703, P30 CA047904, and P50 CA090440-Lung Cancer Developmental Research Award, as well as the American Lung Association Lung Cancer Discovery Award LCD 259111-N and American Cancer Society Fellowship PF-12-081-01-TBG.

Publisher Copyright:
© 2017 AACR.


Dive into the research topics of 'Myeloid STAT3 promotes lung tumorigenesis by transforming tumor immunosurveillance into tumor-promoting inflammation'. Together they form a unique fingerprint.

Cite this