Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer

• Published in: Scientific reports 2025-01, Vol.15 (1), p.2577-9, Article 2577
• Main Authors: Kuribayashi, Tadahiro, Kinoshita, Rie, Ninomiya, Kiichiro, Makimoto, Go, Kubo, Toshio, Rai, Kammei, Ichihara, Eiki, Hotta, Katsuyuki, Tabata, Masahiro, Maeda, Yoshinobu, Kiura, Katsuyuki, Toyooka, Shinichi, Sakaguchi, Masakiyo, Ohashi, Kadoaki
• Format: Article
• Language: English
• Subjects: 692/4028; 692/53; 692/699/1785; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - blood; Blood levels; Calgranulin A - blood; Calgranulin B - blood; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Female; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Metastases; Middle Aged; multidisciplinary; Multivariate analysis; Neoplasm Staging; Non-small cell lung carcinoma; Patients; Plasma; Plasma levels; Prognosis; S100A8/A9; Science; Science (multidisciplinary); Small cell lung carcinoma; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-87232-z

Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital. The pre-treatment plasma levels of S100A8/A9 were analyzed. Eighty-one eligible patients were included (median age, 69 years). Sixty-two patients were men, 54 had adenocarcinoma, 74 had performance status (PS) 0–1, and 47 received ICIs as first-line treatment. The median time to treatment failure (TTF) for ICIs was 5.7 months, and the median overall survival (OS) was 19.6 months. The TTF and OS were worse in patients with high plasma S100A8/A9 levels (≥ 2.475 µg/mL) (median TTF: 4.3 vs. 8.5 months, p  = 0.009; median OS: 15.4 vs. 38.0 months, p  = 0.001). Multivariate analysis revealed that PS ≥ 2, liver metastasis, and high plasma S100A8/A9 levels were significantly associated with short TTF and OS. In conclusion, plasma S100A8/A9 level may have a limited effect on ICI therapy for NSCLC.