{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:15:27Z","timestamp":1787728527204,"version":"build-2784847793"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Cancer-testis antigens (CTAs) are tumor antigens that are normally expressed in the testes but are aberrantly expressed in several cancers. CTA overexpression drives the metastasis and progression of lung cancer, and is associated with poor prognosis. To improve lung cancer diagnosis, prognostic prediction, and drug discovery, robust CTA identification and quantitation is needed. In this study, we examined and quantified the co-expression of CTAs in lung cancer to derive cancer testis antigen burden (CTAB), a novel biomarker of immunotherapy response.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Formalin fixed paraffin embedded (FFPE) tumor samples in discovery cohort (n\u2009=\u20095250) and immunotherapy and combination therapy treated non-small cell lung cancer (NSCLC) retrospective (n\u2009=\u2009250) cohorts were tested by comprehensive genomic and immune profiling (CGIP), including tumor mutational burden (TMB) and the mRNA expression of 17 CTAs. PD-L1 expression was evaluated by IHC. CTA expression was summed to derive the CTAB score. The median CTAB score for the discovery cohort of 170 was applied to the retrospective cohort as cutoff for CTAB \u201chigh\u201d and \u201clow\u201d. Biomarker and gene expression correlation was measured by Spearman correlation. Kaplan\u2013Meier survival analyses were used to detect overall survival (OS) differences, and objective response rate (ORR) based on RECIST criteria was compared using Fisher\u2019s exact test.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The CTAs were highly co-expressed (p\u2009&lt;\u20090.05) in the discovery cohort. There was no correlation between CTAB and PD-L1 expression (R\u2009=\u20090.011, p\u2009=\u20090.45) but some correlation with TMB (R\u2009=\u20090.11, p\u2009=\u20099.2\u2009\u00d7\u200910<jats:sup>\u201314<\/jats:sup>). Kaplan\u2013Meier survival analysis of the immunotherapy-treated NSCLC cohort revealed better OS for the pembrolizumab monotherapy treated patients with high CTAB (p\u2009=\u20090.027). The combination group demonstrated improved OS compared to pembrolizumab monotherapy group (p\u2009=\u20090.04). The pembrolizumab monotherapy patients with high CTAB had a greater ORR than the combination therapy group (p\u2009=\u20090.02).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>CTA co-expression can be reliably measured using CGIP in solid tumors. As a biomarker, CTAB appears to be independent from PD-L1 expression, suggesting that CTAB represents aspects of tumor immunogenicity not measured by current standard of care testing. Improved OS and ORR for high CTAB NSCLC patients treated with pembrolizumab monotherapy suggests a unique underlying aspect of immune response to these tumor antigens that needs further investigation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-024-04918-0","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T16:02:19Z","timestamp":1707321739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer"],"prefix":"10.1186","volume":"22","author":[{"given":"R. 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The WCG IRB determined this study met requirements for a waiver of informed consent under 45 CFR 46 116(f)(2018 Requirements) and 45 CFR 46.116(d) (Pre-2018 Requirements).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RJS, MFS, EVR, SG, PD, MKN, DPD, SZ, JMC, and SP are employees of OmniSeq (Labcorp Oncology), a division of Labcorp. HK, SBH, KCS, RAP, TJJ, EAS, and SR are employees of Labcorp Oncology, a division of Labcorp. ME and BJC are employees of Labcorp. RJS, EVR, SG, SP, and JMC are listed as authors on a pending patent entitled Methods and systems for analyzing and utilizing cancer testis antigen burden.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"141"}}