For Breast Cancer Prognosis, Immunoglobulin Kappa Chain Surfaces to the Top

Whiteside, Theresa L.; Ferrone, Soldano

doi:10.1158/1078-0432.ccr-12-0566

Cited by 46 publications

(41 citation statements)

References 12 publications

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“…tumor-infiltrated B cells as evidenced by the detection of IgG mRNAs in tumors (33,34). Although the pro-or anticancer actions of tumor-infiltrated B cells are controversial based on different studies and clinical conditions (35)(36)(37), it is clear that B lymphocytes are important contributors to host immunity within the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Zhang

Deng

Fan

et al. 2015

Clinical Cancer Research

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Purpose: Studies have demonstrated that cancer-associated matrix metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge region of immunoglobulin G 1 (IgG1). This study investigated the cleavage of endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the IgG hinge cleavage for humoral immunity.Experimental Design: We investigated the occurrence of single peptide bond cleaved IgGs (scIgG) in tumor tissues and plasma samples collected from a cohort of breast cancer patients (n ¼ 60). Samples from healthy people (n ¼ 20) were used as the control. Antibody hinge cleavage was detected by multiple assays, including IHC, ELISA, and flow cytometry. A correlation analysis was conducted between scIgG levels and patient clinical parameters.Results: Levels of scIgGs in tumors were significantly higher than in normal tissues. In addition, scIgG levels in tumors were enriched compared with that in the plasma of the same patients. The appearance of scIgGs in tumor tissues was associated with altered host IgG content and decreased IgG1. Increased tumor scIgGs were found to be positively correlated with adverse clinical factors, such as elevated tumor-associated macrophages, increased expression of MMP9 and other MMPs, and local metastasis to axillary lymph nodes.Conclusions: The study contributes to mounting evidence for the presence of hinge-cleaved antibodies with reduced Fc immune effector function in the tumor microenvironment. The results highlight a link between tumor scIgGs and poor patient outcomes, and reveal a component of compromised humoral immunity within tumors that could point to new immunotherapeutic strategies to rescue host immunity. Clin Cancer Res; 21(23); 5380-90.Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Zhang

Deng

Fan

et al. 2015

Clinical Cancer Research

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“…For example, SERPINA3 was found to be up-regulated in HLA-positive tumors [44]. The IGKC was validated as an immunologic biomarker of prognosis and response to therapy in human breast cancer and other cancers [45]. FETUB may potentially be useful for the treatment of diseases characterized by excess angiogenesis [46].…”

Section: Discussionmentioning

confidence: 99%

Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ –MALDI-MS/MS

He¹,

Wang²,

W³

et al. 2014

neo

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Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression.

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“…Biomarkers that help to decide whether patients benefit from chemotherapy are urgently needed in oncology 19 . Today, only a few such markers are available, and none fits into the immune marker category 19 .…”

Section: Igkc Predicts Response To Neoadjuvant Chemotherapy In Breastmentioning

confidence: 99%

Immunoglobulin kappa chain as an immunologic biomarker of prognosis and chemotherapy response in solid tumors

Schmidt¹,

Micke

Gehrmann

et al. 2012

OncoImmunology

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For Breast Cancer Prognosis, Immunoglobulin Kappa Chain Surfaces to the Top

Cited by 46 publications

References 12 publications

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity

Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ –MALDI-MS/MS

Immunoglobulin kappa chain as an immunologic biomarker of prognosis and chemotherapy response in solid tumors

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