Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma

Aram A Musaelyan; Sergey V Lapin; Margarita A Urtenova; Svetlana V Odintsova; Ivan V Chistyakov; Andrey M Ulitin; Andrey L Akopov; Sergey V Orlov

doi:10.3892/etm.2022.11495

Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma

Exp Ther Med. 2022 Jul 5;24(3):557. doi: 10.3892/etm.2022.11495. eCollection 2022 Sep.

Authors

Aram A Musaelyan^{1

2}, Sergey V Lapin¹, Margarita A Urtenova³, Svetlana V Odintsova³, Ivan V Chistyakov⁴, Andrey M Ulitin³, Andrey L Akopov⁴, Sergey V Orlov^{3

5}

Affiliations

¹ Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine, Pavlov First Saint Petersburg State Medical University, Saint Petersburg 197022, Russia.
² Laboratory for Molecular biology, Research Institute of Medical Primatology, Veseloe, Sochi, Krasnodar Territory 354376, Russia.
³ Department of Clinical Oncology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg 197022, Russia.
⁴ Department of Thoracic Surgery, Pavlov First Saint Petersburg State Medical University, Saint Petersburg 197022, Russia.
⁵ Administration, Research Institute of Medical Primatology, Veseloe, Sochi, Krasnodar Territory 354376, Russia.

Abstract

Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy. In groups 1 and 2 β-2 microglobulin (B2-MG), neopterin (NPT), IL-6, IL-18, HLA-DRB1 and autoantibodies were assessed after two months of ICI, and before the start of next administration in group 3. In group 1 low level of B2-MG (P<0.0001), NPT (P<0.0001), IL-6 (P<0.0001), IL-18 (P=0.0003), HLA-DRB1*03 (P=0.016) and anti-TPO antibodies (P=0.016) were associated with response >six months. In group 2 high level of B2-MG (P=0.0001), NPT (P=0.0016), IL-6 (P=0.013) and IL-18 (P=0.032) were associated with early disease progression (<six months). Univariate analysis demonstrated that immune-related adverse events were predictive marker of prolonged progression-free survival (PFS) in group 1 (P=0.038) and 2 (P=0.020). Neutrophil-lymphocyte ratio ≥5 before immunotherapy was correlated with shorter PFS in melanoma in multivariate analysis (P=0.007). B2-MG ≥2.5 mg/ml (P=0.006) and NPT ≥12 nmol/l (P=0.027) were predictors of shorter PFS in group 1. B2-MG ≥2.5 mg/ml was predictor of shorter PFS (P=0.008) in group 2. In group 1 levels of B2-MG, NPT, IL-6 and IL-18 were higher than in group 3. In summary, immunological markers are promising predictive markers for immunotherapy; however, it requires further prospective studies.

Keywords: HLA-DRB1; autoantibodies; immune checkpoint inhibitors; immune-related adverse events; interleukin-18; interleukin-6; neopterin; neutrophil-to-lymphocyte ratio; peripheral blood biomarker; β-2 microglobulin.

Grants and funding

Funding: No funding was received.