RRC ID 64566
Author Atsumi S, Katoh H, Komura D, Hashimoto I, Furuya G, Koda H, Konishi H, Suzuki R, Yamamoto A, Yuba S, Abe H, Rino Y, Oshima T, Ushiku T, Fukayama M, Seto Y, Ishikawa S.
Title Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases.
Journal Commun Biol
Abstract Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.
Volume 3(1)
Pages 588
Published 2020-10-16
DOI 10.1038/s42003-020-01305-5
PII 10.1038/s42003-020-01305-5
PMID 33067514
PMC PMC7567837
MeSH Antigens, Neoplasm / immunology* Autoantigens / immunology* Autoimmune Diseases / etiology* Autoimmune Diseases / metabolism* B-Lymphocytes / immunology B-Lymphocytes / metabolism Binding Sites Epitopes, B-Lymphocyte / immunology Fluorescent Antibody Technique Focal Adhesions* Humans Immunity, Humoral Models, Biological Multiprotein Complexes / metabolism* Neoplasms / immunology Neoplasms / metabolism Neoplasms / pathology Nucleotide Motifs Protein Binding / immunology Receptors, Antigen, B-Cell / metabolism Ribonucleoproteins / metabolism* Tumor Microenvironment / immunology
IF 3.998
Resource
Human and Animal Cells PANC-1(RCB2095)