Automated immunoassay of serum NY-ESO-1 and XAGE1 antibodies for predicting clinical benefit with immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer

• Published in: Cancer treatment and research communications 2024, Vol.40, p.100830, Article 100830
• Main Authors: Sakaeda, Kanako, Kurose, Koji, Matsumura, Yuki, Muto, Satoshi, Fukuda, Minoru, Sugasaki, Nanae, Fukuda, Masaaki, Takemoto, Shinnosuke, Taniguchi, Hirokazu, Masuda, Takeshi, Shimizu, Katsuhiko, Kataoka, Yuki, Irino, Yasuhiro, Sakai, Yumiko, Atarashi, Yusuke, Yanagida, Masatoshi, Hattori, Noboru, Mukae, Hiroshi, Nakata, Masao, Kanda, Eiichiro, Oga, Toru, Suzuki, Hiroyuki, Oka, Mikio
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - immunology; Autoantibody; Biomarker; Biomarkers, Tumor - blood; Cancer/testis antigen; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Female; Humans; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunoassay - methods; Immunotherapy; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Male; Membrane Proteins - genetics; Middle Aged; Nivolumab - therapeutic use; Retrospective Studies; Tertiary lymphoid structures
• ISSN: 2468-2942; 2468-2942
• DOI: 10.1016/j.ctarc.2024.100830

[Display omitted] •NY-ESO-1 and XAGE1 cancer/testis antigens are highly immunogenic in NSCLC patients.•NY-ESO-1/XAGE1 Abs are potentially antitumor B-cell and T-cell markers in NSCLC.•We developed an automated immunoassay system measuring serum NY-ESO-1/XAGE1 abs.•Our immunoassay of NY-ESO-1/XAGE1 Abs predicted the clinical benefit with nivolumab.•Our immunoassay is probably useful in clinical practice of ICI therapy for NSCLC. NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11). Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.