In contrast to its potential role in tumor growth and spread, it also has been shown that HMGB1-induced TLR4 signaling is required for effective responses to chemo-radiation in established tumors in animal models (107) . These findings are validated further by the observation that node positive breast cancer patients carrying a loss of function TLR4 allele tend to relapse more quickly after treatment with chemo-radiation as compared to patients with wild-type TLR4 alleles (107, 108) . More recently, HMGB1 has been recognized as a tumor derived DAMP capable of recruiting and activating eosinophils. The role of tumor infiltrating eosinophils is still being elucidated as they can either limit tumor growth through destructive effector functions or promote tumor growth through immunoregulation and tissue repair/remodeling (109, 110) .