Secreted Tumor Antigens – Immune Biomarkers for Diagnosis and Therapy

Abstract

With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through e.g. genetic mutations (neoantigens), protein truncation, protein misfolding, or abnormal posttranslational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies. Cytotoxic T cells are thought to be responsible for killing of tumor cells, and several recent studies have used MS, combined with exome/transcriptome sequencing and bioinformatics, to identify their cognate peptide ligands on tumor MHC class I molecules. Circulating (serum) antibodies have been more widely used to identify tumor antigens in a range of human cancers, using 2D Western blots, immunoaffinity, and microarray technologies. More specific antibody probes have been generated by harvesting antibodies directly from antibody-secreting cells through in vitro cultures of lymph node cells (antibody-secreting cells probes) or B-cell immortalization. Further identification and characterization of tumor antigens is likely to have important implications for cancer diagnostic and biomarker discovery, immune profiling, and the development of cancer vaccines and targeted immunotherapies.

The role of protein disulphide isomerase AGR2 in the tumour niche

“…Third, it can lead to remodelling of the immune response in the tumour microenvironment [Paltridge et al., ]. Fourth, it can modulate tumour immunogenicity by secreting tumour antigens into the tumour niche [Meeusen et al., ]. In course of tumorigenesis, the regulation of protein homoeostasis (proteostasis) is strongly involved in cellular maintenance.…”

Immunoprofiling of Breast Cancer Antigens Using Antibodies Derived from Local Lymph Nodes

“…An antitumor immune response, generated naturally or through vaccination, is critically dependent on the presence of tumor antigens generated during cancer formation. Tumor antigens expressed on the surface of tumor cells can also provide attractive targets for new and personalized immunotherapy approaches [3,4]. A major effort is therefore being directed towards identifying tumor antigens expressed by individual cancer patients.…”

Prognostic Value of Circulating IGFBP2 and Related Autoantibodies in Children with Metastatic Rhabdomyosarcomas

“…TAABs, in turn, can be used to define a unique cancer signature, as they sense changes in cellular protein expression and monitor the evolutionary dynamics of the tumor. TAABs are of particular interest as cancer biomarkers, as they can be easily isolated from blood, are more stable than antigens and their response is enduring and detectable even when triggered by a relatively small amount of antigen [35][36][37].…”