LL-37 Recruits Immunosuppressive Regulatory T Cells to Ovarian Tumors

摘要

Histological examination of ovarian, breast, and lung tumors has shown that the pro-inflammatory peptide, LL-37, is abnormally elevated. LL-37 was originally identified as one of the host defense peptides that is released during infections to attack microorganisms. Recent studies established other functions for LLin immune responses, tissue injury and inflammation. LL-37 is highly elevated at sites of inflammation and wound healing where it is a mitogen and proangiogenic factor. LL-37 also acts as a potent chemoattractant for various immune cells. In contrast to LL-37's established functions in host defense and tissue damage, its role in the tumor microenvironment and the advantage given to tumor cells by its and its receptor's expression is not entirely clear. Our studies indicate that LL-37's functions are multifaceted in solid tumors, where evidence exists for its role as a mitogen, pro-angiogenic factor, and leukocyte chemoattractant. Specifically we were first to show that: LL-37 levels are highly elevated in ovarian cancer when compared to normal ovarian tissue. LL-37 specifically affects the growth and spread of ovarian cancer cells. LL37 in the ovarian cancer tumors specifically recruits mesenchymal stem cells (MSC). MSCs recruited to the cancer microenvironment promote tumor growth and spread.