title: Tissue damage-associated "danger signals" influence T-cell responses that promote the progression of preneoplasia to cancer.
abstract: T-cell responses may be shaped by sterile "danger signals" that are constituted by damage-associated molecular patterns (DAMP). However, whether and what type of adaptive immune responses are triggered in vivo by DAMPs induced by tumor progression are not well characterized. In this study, we report that the production of HMGB1, an established DAMP released by dying cells, was critical for tumor progression in an established mouse model of prostate cancer. HMGB1 was required for the activation and intratumoral accumulation of T cells that expressed cytokine lymphotoxinα(1)β(2) (LT) on their surface. Intriguingly, these tumor-activated T cells recruited macrophages to the lesion and were essential to promote the preneoplasia to invasive carcinoma in an LTβ receptor (LTβR)-dependent manner. Taken together, our findings suggest that the release of HMGB1 as an endogenous danger signal is important for priming an adaptive immune response that promotes malignant progression, with implications for cancer prevention and therapy.
authors.affiliation: The Committee on Immunology and Section of Dermatology/Department of Medicine University of Chicago, Chicago 60637, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Jikun
authors.initials: J
authors.lastname: Zha
authors.forename: Yamin
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.forename: Xuanming
authors.initials: X
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018450:Disease Progression; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D053308:Lymphotoxin-beta / Q000378:metabolism; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein; D053308:Lymphotoxin-beta