Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer.

Autor: Seager RJ; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Senosain MF; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Van Roey E; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Gao S; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., DePietro P; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Nesline MK; Labcorp Oncology, Durham, NC, USA., Dash DP; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Zhang S; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Ko H; Labcorp Oncology, Durham, NC, USA., Hastings SB; Labcorp Oncology, Durham, NC, USA., Strickland KC; Labcorp Oncology, Durham, NC, USA.; Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA., Previs RA; Labcorp Oncology, Durham, NC, USA.; Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA., Jensen TJ; Labcorp Oncology, Durham, NC, USA., Eisenberg M; Labcorp, Burlington, NC, USA., Caveney BJ; Labcorp, Burlington, NC, USA., Severson EA; Labcorp Oncology, Durham, NC, USA., Ramkissoon S; Labcorp Oncology, Durham, NC, USA.; Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA., Conroy JM; OmniSeq (Labcorp Oncology), Buffalo, NY, USA., Pabla S; OmniSeq (Labcorp Oncology), Buffalo, NY, USA. pablas@labcorp.com.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2024 Feb 07; Vol. 22 (1), pp. 141. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1186/s12967-024-04918-0
Abstrakt: Background: 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.
Methods: Formalin fixed paraffin embedded (FFPE) tumor samples in discovery cohort (n = 5250) and immunotherapy and combination therapy treated non-small cell lung cancer (NSCLC) retrospective (n = 250) 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 "high" and "low". Biomarker and gene expression correlation was measured by Spearman correlation. Kaplan-Meier survival analyses were used to detect overall survival (OS) differences, and objective response rate (ORR) based on RECIST criteria was compared using Fisher's exact test.
Results: The CTAs were highly co-expressed (p < 0.05) in the discovery cohort. There was no correlation between CTAB and PD-L1 expression (R = 0.011, p = 0.45) but some correlation with TMB (R = 0.11, p = 9.2 × 10 -14 ). Kaplan-Meier survival analysis of the immunotherapy-treated NSCLC cohort revealed better OS for the pembrolizumab monotherapy treated patients with high CTAB (p = 0.027). The combination group demonstrated improved OS compared to pembrolizumab monotherapy group (p = 0.04). The pembrolizumab monotherapy patients with high CTAB had a greater ORR than the combination therapy group (p = 0.02).
Conclusions: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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