Characterization of MHC Class I and β‐2‐Microglobulin Expression in Pediatric Solid Malignancies to Guide Selection of Immune‐Based Therapeutic Trials. Issue 4 (17th November 2015)

• Record Type: Journal Article
• Authors: Haworth, Kellie B.; Arnold, Michael A.; Pierson, Christopher R.; Leddon, Jennifer L.; Kurmashev, Dias K.; Swain, Hayley M.; Hutzen, Brian J.; Roberts, Ryan D.; Cripe, Timothy P.
• Is Part Of: Pediatric blood & cancer. Volume 63:Issue 4(2016)
• Page Start: 618
• Page End: 626
• Publication Date: 2015-11-17
• Subjects: immunophenotype -- immunotherapy -- MHC class I -- pediatric oncology -- solid tumors -- tumor biology; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.25842
• Languages: English
• ISSNs: 1545-5009

Abstract

Abstract : Background: Over 10, 000 US children are diagnosed with cancer yearly. Though outcomes have improved by optimizing conventional therapies, recent immunotherapeutic successes in adult cancers are emerging. Cytotoxic T lymphocytes (CTLs) are the primary executioners of adaptive antitumor immunity and require antigenic presentation in the context of major histocompatibility complex (MHC) class I and the associated β‐2‐microglobulin (B2M). Loss of MHC I expression is a common immune escape mechanism in adult malignancies, but pediatric cancers have not been thoroughly characterized. The essential nature of MHC I expression in CTL‐mediated cell death may dictate the success of immunotherapies, which rely on eliciting an adaptive response. Procedure: We queried pediatric tumor microarray databases for MHC I and B2M gene expression. We detected MHC I in pediatric tumor cell lines by flow cytometry and characterized MHC I and B2M expression in patient samples by immunohistochemistry. To determine whether therapeutic approaches might enhance MHC I expression in selected models in vitro, we tested effects of exposure to IFN‐γ and histone deacetylase inhibitors. Results: Pediatric tumors overall, as well as samples within select individual tumor subtypes, exhibit wide ranges of MHC I and B2M gene and protein expression. For most cell lines tested, MHC I was inducible in vitro . Conclusions: MHC I and B2M expression vary among pediatric tumor types and should be evaluated as potential biomarkers, which might identify patients most likely to benefit from MHC I dependent immunotherapies. Modulation of MHC I expression may be a promising mechanism for enhancing MHC I dependent immunotherapeutic efficacy.