Abstract
Tumor antigens are responsible for initiating an immune response in cancer patients, and their identification may provide new biomarkers for cancer diagnosis and targets for immunotherapy. The general use of serum antibodies to identify tumor antigens has several drawbacks, including dilution, complex formation, and background reactivity. In this study, antibodies were generated from antibody-secreting cells (ASC) present in tumor-draining lymph nodes of 20 breast cancer patients (ASC-probes) and were used to screen breast cancer cell lines and protein microarrays. Half of the ASC-probes reacted strongly against extracts of the MCF-7 breast cancer cell line, but each with a distinct antigen recognition profile. Three of the positive ASC-probes reacted differentially with recombinant antigens on a microarray containing cancer-related proteins. The results of this study show that lymph node-derived ASC-probes provide a highly specific source of tumor-specific antibodies. Each breast cancer patient reacts with a different antibody profile which indicates that targeted immunotherapies may need to be personalized for individual patients. Focused microarrays in combination with ASC-probes may be useful in providing immune profiles and identifying tumor antigens of individual cancer patients.
Highlights
Immunotherapy has changed the landscape of cancer treatment for an increasing number of solid tumors and has increased interest in the immunological status of cancer patients [1,2]
The lymph node processed for antibody-secreting cell (ASC)-probe 3 was macroscopically assessed to contain a tumor, and ASC-probe 6 was produced from a pool of large lymph nodes from the only patient with occult primary cancer
All reactive ASC-probes showed a unique pattern of band reactivity, some bands appear shared amongst several samples
Summary
Immunotherapy has changed the landscape of cancer treatment for an increasing number of solid tumors and has increased interest in the immunological status of cancer patients [1,2]. Tumor antigens expressed on the surface of tumor cells can provide attractive targets for new and personalized immunotherapy approaches [3,4]. Tumor antigens are recognized by both T and B cell receptors, in different formats (peptide vs native molecule), and most B cell responses require T cell help for clonal expansion and the generation of antibody-secreting cells (ASCs) [5]. The initial interactions between antigen-presenting cells and T and B cells takes place in the lymph nodes draining the target tissues and result in the production of antigen-specific ASCs. Fully differentiated ASCs can secrete thousands of antibody molecules per second [6] and provide a significant biological amplification of molecular changes occurring in cancer cells and a reflection of the tumor’s antigenic profile. Antibodies produced by ASCs are released into the blood stream, where they are vastly diluted with nonspecific antibodies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
