标题：Lack of interferon-gamma receptor results in a microenvironment favorable for intestinal tumorigenesis
作者：Zhang, Caibo; Hou, Dong; Wei, Haifeng; Zhao, Minnan; Yang, Lin; Liu, Qiao; Zhang, Xiyu; Gong, Yaoqin; Shao, Changshun
作者机构：[Zhang, Caibo; Hou, Dong; Zhao, Minnan; Liu, Qiao; Zhang, Xiyu; Gong, Yaoqin; Shao, Changshun] Shandong Univ, Key Lab Expt Teratol, Minist Educ, Sch M 更多
通讯作者：Shao, CS;Shao, CS;Shao, CS
通讯作者地址：[Shao, CS]Shandong Univ, Key Lab Expt Teratol, Minist Educ, Sch Med, Jinan 250012, Shandong, Peoples R China;[Shao, CS]Shandong Univ, Dept Mol Med & G 更多
关键词：IFN-gamma receptor; intestinal tumorigenesis; gene expression profiling;; inflammation; tumor microenvironment
摘要：IFN-gamma plays an important role in innate and adaptive immunity. IFN-gamma signaling is also involved in tumorigenesis, with both pro- and antitumor activities documented. We here report the characterization of intestinal tumorigenesis in Apc(Min/+) mice that lack IFN-gamma receptor. We observed that Ifngr1(-/-)Apc(Min/+) mice are shorter-lived than Ifngr(1+/+)Apc(Min/+) mice. The tumors in Ifngr(1-/-)Apc(Min/+) mice are more likely to progress into invasive adenocarcinomas. Gene expression profiling by RNA sequencing revealed a significant upregulation of genes involved in inflammation and tissue remodeling in tumors of Ifngr1(-/-)Apc(Min/+) mice when compared to those in Ifngr1(+/+)Apc(Min/+) mice. In particular, five genes encoding matrix metallopeptidases (MMPs) were among the upregulated. On the other hand, genes that promote or maintain intestinal differentiation, such as Cdx2, Cdhr2 and Cdhr5, were downregulated. Tumorassociated macrophages were more abundant and were more favored toward M2 polarization in Ifngr1(-/-)Apc(Min/+) mice than in Ifngr1(+/+)Apc(Min/+) mice. Furthermore, the Ifngr1 was significantly downregulated in intestinal tumors when compared to mucosa. A similar trend was noted for human colorectal carcinomas. Together, our results indicate that adequate IFN-gamma signaling is critical for maintaining a tumor-prohibitive microenvironment.