Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study.
Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., "focused cancer immunotherapy") based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n = 28), colon (n = 20), bladder (n = 20), renal cell (n = 15) and malignant lymphoma (n = 9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter-alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients.
Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.|Nagasaki University Research Centre for Genomic Instability and Carcinogenesis (NRGIC), Nagasaki, Japan.
Kaname
K
Ohyama
Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Haruka
H
Yoshimi
Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Nozomi
N
Aibara
Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki University, Nagasaki, Japan.
Yoichi
Y
Nakamura
Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Yasuyoshi
Y
Miyata
Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Hideki
H
Sakai
Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Fumihiko
F
Fujita
Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Yoshitaka
Y
Imaizumi
Division of Adult and Pediatric Rheumatology, Saint Louis University School of Medicine, St. Louis, MO.
Anil K
AK
Chauhan
Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Naoya
N
Kishikawa
Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Naotaka
N
Kuroda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000510:Alpha-Globulins / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D005260:Female; D018260:Gelsolin / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology
D000510:Alpha-Globulins; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D018260:Gelsolin; D010750:Phosphoproteins; C011877:inter-alpha-inhibitor
gelsolin; immune complex; lung cancer; mass spectrometry