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Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study
Author(s) -
Ohyama Kaname,
Yoshimi Haruka,
Aibara Nozomi,
Nakamura Yoichi,
Miyata Yasuyoshi,
Sakai Hideki,
Fujita Fumihiko,
Imaizumi Yoshitaka,
Chauhan Anil K,
Kishikawa Naoya,
Kuroda Naotaka
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30455
Subject(s) - immune system , antigen , lung cancer , immunology , cancer , medicine , biology , cancer research , oncology , genetics
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.