The immune system is the major defense against tumorigenesis and tumor progression. However, many tumors acquire the ability to blunt or even invert the functions of the immune system. We are interested in the question of how breast cancers evolve to alter the immune system both systemically and locally. In particular, we aim to delineate how this is happening in the complex tumor ecosystems that differ between patients. The questions we are trying to attack include: 1) how the systemic and local immune environment varies among tumors of diverse genetic/epigenetic background; 2) how different tumors and immune cells co-evolve to develop diverse ecosystems; and 3) how to identify and target immune cell types/functions that confer therapeutic vulnerability in a specific tumor ecosystem. Our ultimate goal is to identify therapies that could restore the normal functions of the immune system.
Immuno-subtyping of breast cancer reveals distinct myeloid cell biology and immunotherapy resistance mechanisms
Ik Sun Kim, Yang Gao, Thomas Welte, Hai Wang, Jun Liu, Mahnaz Janghorban, Kuanwei Sheng, YichiNiu, Amit Goldstein, Na Zhao, Igor Bado, Hin-Ching Lo, Michael J. Toneff, Tuan Nguyen, Wen Bu, Weiyu Jiang, ..., Jeffrey M. Rosen, Xiang H.-F. Zhang. (2019) Nature Cell Biology 18(6), 632-644. [DOI]
Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming
Lin Tian, Amit Goldstein, Hai Wang, Hin Ching Lo, Ik Sun Kim, Thomas Welte, Kuanwei Sheng, Lacey E. Dobrolecki, Xiaomei Zhang, Nagireddy Putluri, Thuy L. Phung, Sendurai A. Mani, Fabio Stossi, Arun Sreekumar, ..., Xiang H.-F. Zhang. (2017) Nature 544(7649):250-254. [DOI]
Oncogenic mTOR signalling recruits myeloid-derived suppressor cells to promote tumour initiation
Thomas Welte, Ik Sun Kim, Lin Tian, Xia Gao, Hai Wang, June Li, Xue B Holdman, Jason I Herschkowitz, ... Xiang H.-F. Zhang. (2016) Nature Cell Biology 18(6), 632-644. [DOI]
Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal.
Hao X, Shen Y, Chen N, Zhang W, Valverde E, Wu L, Chan HL, Xu Z, Yu L, Gao Y, Bado I, Michie LN, Rivas CH, Becerra-Dominguez L, Aguirre S, Pingel BC, Wu Y-H, Liu F, Ding Y, Edwards DG, Liu J, ..., Xiang H.-F. Zhang. (2023) Cell Stem Cell Volume 30, Issue 5, 4 May 2023, Pages 648-664.e8. [PDF] [DOI] [PubMed]
Resistance to natural killer cell immunosurveillance confers a selective advantage to polyclonal metastasis
Hin Ching Lo, Zhan Xu, Ik Sun Kim, Bradley Pingel, Sergio Aguirre, Srikanth Kodali, Jun Liu, Weijie Zhang, Aaron M. Muscarella, Sarah M. Hein, Alexander S. Krupnick, Joel R. Neilson, Silke Paust, Jeffrey M. Rosen, Hai Wang & Xiang H.-F. Zhang. (2020) Nature Cancer 1, 709–722. [DOI]