title: The Alarmin HMGN1 contributes to antitumor immunity and is a potent immunoadjuvant.
abstract: Alarmins are endogenous mediators that are elicited rapidly in response to danger signals, enhancing innate and adaptive immune responses by promoting the recruitment and maturation of antigen-presenting cells (APC). The nucleosome-binding protein HMGN1 is a potent alarmin that binds TLR4 and induces antigen-specific Th1 immune responses, but its contributions to antitumor immunity have not been explored. We found that ovalbumin (OVA)-expressing EG7 mouse thymoma cells grew much faster in Hmgn1-deficient mice than littermate-matched controls. Tumor-bearing Hmgn1(-/-) mice generated fewer OVA-specific CD8 cells in the spleen than EG7-bearing Hmgn1(+/+) mice, suggesting that HMGN1 supported T cell-mediated antitumor immunity. In addition, EG7 tumors expressing HMGN1 grew more slowly than control EG7 tumors, suggesting greater resistance to HMGN1-expressing tumors. This resistance relied on T cell-mediated immunity because it was abolished by in vivo depletion of CD4(+) and CD8(+) T cells. Moreover, mice vaccinated with a DNA vector expressing an HMGN1-gp100 fusion protein manifested gp100-specific, Th1-polarized immune responses, acquiring resistance to challenge with mouse B16F1 melanoma. Overall, our findings show that HMGN1 contributes to antitumor immunity and it may offer an effective adjuvant to heighten responses to cancer vaccines.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland. Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Basic Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland. dyang@mail.nih.gov.
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland. Basic Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland.
authors.forename: Poonam
authors.initials: P
authors.lastname: Tewary
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland.
authors.forename: Yana
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland. Basic Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland.
authors.forename: O M Zack
authors.initials: OM
authors.lastname: Howard
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland.
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D024241:HMGN1 Protein / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014611:Vaccination; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D024241:HMGN1 Protein; D011993:Recombinant Fusion Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D058951:gp100 Melanoma Antigen