Journal article
Authors list: Zheng, Xiang; Sarode, Poonam; Weigert, Andreas; Turkowski, Kati; Chelladurai, Prakash; Guenther, Stefan; Kuenne, Carsten; Winter, Hauke; Stenzinger, Albrecht; Reu, Simone; Grimminger, Friedrich; Stiewe, Thorsten; Seeger, Werner; Pullamsetti, Soni Savai; Savai, Rajkumar
Publication year: 2023
Pages: 2345-2357
Journal: Cancer Research
Volume number: 83
Issue number: 14
ISSN: 0008-5472
eISSN: 1538-7445
Open access status: Green
DOI Link: https://doi.org/10.1158/0008-5472.CAN-22-1270
Publisher: American Association for Cancer Research
Abstract:
Tumor-associated macrophages (TAM), including antitumor M1-like TAMs and protumor M2-like TAMs, are transcriptionally dynamic innate immune cells with diverse roles in lung cancer development. Epigenetic regulators are key in controlling macro-phage fate in the heterogeneous tumor microenvironment. Here, we demonstrate that the spatial proximity of HDAC2-overexpressing M2-like TAMs to tumor cells signiflcantly correlates with poor overall survival of lung cancer patients. Suppression of HDAC2 in TAMs altered macrophage phenotype, migration, and signaling pathways related to interleukins, chemokines, cytokines, and T-cell activation. In coculture systems of TAMs and cancer cells, suppres-sing HDAC2 in TAMs resulted in reduced proliferation and migration, increased apoptosis of cancer cell lines and primary lung cancer cells, and attenuated endothelial cell tube formation. HDAC2 regulated the M2-like TAM phenotype via acetylation of histone H3 and transcription factor SP1. Myeloid cell-speciflc deletion of Hdac2 and pharmacologic inhibition of class I HDACs in four different murine lung cancer models induced the switch from M2-like to M1-like TAMs, altered inflltration of CD4thorn and CD8thorn T cells, and reduced tumor growth and angiogenesis. TAM-speciflc HDAC2 expression may provide a biomarker for lung cancer stratiflcation and a target for developing improved thera-peutic approaches.
Citation Styles
Harvard Citation style: Zheng, X., Sarode, P., Weigert, A., Turkowski, K., Chelladurai, P., Guenther, S., et al. (2023) The HDAC2-SP1 Axis Orchestrates Protumor Macrophage Polarization, Cancer Research, 83(14), pp. 2345-2357. https://doi.org/10.1158/0008-5472.CAN-22-1270
APA Citation style: Zheng, X., Sarode, P., Weigert, A., Turkowski, K., Chelladurai, P., Guenther, S., Kuenne, C., Winter, H., Stenzinger, A., Reu, S., Grimminger, F., Stiewe, T., Seeger, W., Pullamsetti, S., & Savai, R. (2023). The HDAC2-SP1 Axis Orchestrates Protumor Macrophage Polarization. Cancer Research. 83(14), 2345-2357. https://doi.org/10.1158/0008-5472.CAN-22-1270
Keywords
APC; BREAST; DEATH; SP1
