Gene and protein expression of MAGE and associated immune landscape elements in non-small-cell lung carcinoma and urothelial carcinomas Journal Article
| Authors: | Faiena, I.; Adhikary, S.; Schweitzer, C.; Astrow, S. H.; Grogan, T.; Funt, S. A.; Bot, A.; Dorff, T.; Rosenberg, J. E.; Elashoff, D. A.; Pantuck, A. J.; Drakaki, A. |
| Article Title: | Gene and protein expression of MAGE and associated immune landscape elements in non-small-cell lung carcinoma and urothelial carcinomas |
| Abstract: | Melanoma-associated antigen-A (MAGE-A) is expressed in multiple cancers with restricted expression in normal tissue. We sought to assess the MAGE-A3/A6 expression profile as well as immune landscape in urothelial (UC) and non-small cell lung carcinoma (NSCLC). We also assessed co-expression of immune-associated markers, including programmed cell death ligand 1 (PDL1) in tumor and/or immune cells, and assessed the effect of checkpoint inhibitor treatment on these markers in the context of urothelial carcinoma. We used formalin-fixed paraffin-embedded (FFPE) tissue sections from a variety of tumor types were screened by IHC for MAGE-A and PD-L1 expression. Gene expression analyses by RNA sequencing were performed on RNA extracted from serial tissue sections. UC tumor samples from patients treated with checkpoint inhibitors were assessed by IHC and NanoString gene expression analysis for MAGE-A and immune marker expression before and after treatment. Overall, 84 samples (57%) had any detectable MAGE-A expression. Detectable MAGE-A expression was present at similar frequencies in both tumor tissue types, with 41 (50%) NSCLC and 43 (64%) UC. MAGE-A expression was not significantly changed before and after checkpoint inhibitor therapy by both IHC and NanoString mRNA sequencing. Other immune markers were similarly unchanged post immune checkpoint inhibitor therapy. Stable expression of MAGEA3/A6 pre and post checkpoint inhibitor treatment indicates that archival specimens harvested after checkpoint therapy are applicable to screening potential candidates for MAGE therapies. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | human tissue; protein expression; aged; middle aged; unclassified drug; major clinical study; genetics; nonhuman; genetic analysis; metabolism; gene; disease association; apoptosis; gene expression; gene expression profiling; carcinoma, non-small-cell lung; lung neoplasms; clinical assessment; neoplasm proteins; tumor antigen; tumor marker; tissue section; lung tumor; gene expression regulation; urologic neoplasms; urothelium; gene expression regulation, neoplastic; immunology; antigens, neoplasm; messenger rna; diagnosis; tumor protein; melanoma antigen; transitional cell carcinoma; adoptive immunotherapy; immunocompetent cell; formaldehyde; stable expression; urothelial; programmed death 1 ligand 1; magea3 protein, human; non small cell lung cancer; paraffin embedding; t-cell therapy; mage; pd-l1; urinary tract tumor; immune checkpoint inhibitor; cancer test; humans; human; male; female; article; rna sequencing; immune checkpoint inhibitors; biomarkers, tumor; melanoma associated antigen a; b7-h1 antigen; checkpoint inhibitor therapy; screening assay; zastumotide; magea6 protein, human |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 47 |
| Issue: | 9 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2024-11-01 |
| Start Page: | 351 |
| End Page: | 360 |
| Language: | English |
| DOI: | 10.1097/cji.0000000000000538 |
| PUBMED: | 39169899 |
| PROVIDER: | scopus |
| PMCID: | PMC11446647 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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