Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study

Abstract

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.

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

“…Apart from the ITIH1 and AMBP, which are generally upregulated [39,45], each member of the ITIH family depicts differential expression levels in various tumors [45]. These proteins (ITIH1 and AMBP) in our research also exhibited increased plasma levels in CRC in stages I and II and displayed FC values of 5.05 and 2.94, respectively (Supplementary Materials Table S4).…”

“…These proteins (ITIH1 and AMBP) in our research also exhibited increased plasma levels in CRC in stages I and II and displayed FC values of 5.05 and 2.94, respectively (Supplementary Materials Table S4). There was no statistically significant difference in the plasma level of ITIHs between various subgroups of CRC patients stratified by clinical characteristics [45]. However, different expression levels were observed for ITIH3 and ITIH4, which were down-and up-regulated, respectively, in CRC patients.…”

“…Recently, the involvement of ITIH in different pathophysiological processes, including inflammation and carcinogenesis, has been discovered and extensively elucidated [43,44]. These proteins are positively or negatively regulated depending on the conditions, but there is certain strong evidence that all ITIH family members play a significant role in cell malignant processes and tumor growth [39,45]. Up until now, there is no systematic approach to evaluating differential abundances of ITIH family proteins in cancer development due to limited sensitivity and specificity, and thus the modality for early detection of CRC is also limited [46].…”

Long‐lasting persistence of large B‐cell clones in hepatitis C virus‐cured patients with complete response of mixed cryoglobulinaemia vasculitis

“…In the cohort reported here, one complete responder had recurrence of purpura and of cryoglobulinaemia in concomitance with an acute respiratory infection; also notably, a lung cancer was diagnosed during antiviral therapy in a patient who had dramatic progression of vasculitis despite the clearance of HCV. Altogether, these cases suggest that abundant immune complexes produced during infections, vaccination or lung cancer might reactivate B‐cell clones leading to the relapse of MCV. Experiments in transgenic mice support the concept that immune complexes can induce pre‐activated, but not naïve, RF‐producing B‐cells to proliferate and secrete antibody .…”

A contribution of FcγRIIIa cosignaling in TFHsubset development in Systemic Lupus Erythematosus

“…ICs are composed of large number of antigenic peptides [47]. Both FDC and/or GC B cells retain ICs on the cell surface, which fulfill the antigenic requirement for T FH development in GC reaction.…”