Gene and Protein Expression of MAGE and Associated Immune Landscape Elements in Non-Small-Cell Lung Carcinoma and Urothelial Carcinomas.

Autor: Faiena I; Columbia University Irving Medical Center, New York, NY., Adhikary S; Kite, A Gilead Company, Santa Monica, CA., Schweitzer C; Kite, A Gilead Company, Santa Monica, CA., Astrow SH; Chimeric Therapeutics, Carlton South, Vic., Australia., Grogan T; Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA., Funt SA; Memorial Sloan Kettering Cancer Center, New York, NY., Bot A; Capstan Therapeutics, San Diego, CA., Dorff T; City of Hope Comprehensive Cancer Center, Duarte, CA., Rosenberg JE; Memorial Sloan Kettering Cancer Center, New York, NY., Elashoff DA; Department of Medicine Statistics Core, David Geffen School of Medicine at UCLA, Los Angeles, CA., Pantuck AJ; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA., Drakaki A; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Jazyk: angličtina
Zdroj: Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2024 Nov-Dec 01; Vol. 47 (9), pp. 351-360. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1097/CJI.0000000000000538
Abstrakt: 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 (PD-L1) 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 MAGE-A3/A6 pre and post checkpoint inhibitor treatment indicates that archival specimens harvested after checkpoint therapy are applicable to screening potential candidates for MAGE therapies.
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Databáze: MEDLINE