M Teresa Agulló-Ortuño1, Óscar Gómez-Martín2, Santiago Ponce3, Lara Iglesias3, Laura Ojeda4, Irene Ferrer4, Inmaculada García-Ruiz2, Luis Paz-Ares5, Virginia Pardo-Marqués2. 1. Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain; Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: agullo@h12o.es. 2. Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. 3. Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Medical Oncology Department Hospital Universitario 12 de Octubre, Madrid, Spain. 4. Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain; Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. 5. Laboratory of Thoracic and Clinical-Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain; Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain; Medical Oncology Department Hospital Universitario 12 de Octubre, Madrid, Spain; Medicine Department, Facultad de Medicina y Cirugía, Universidad Complutense de Madrid (UCM), Madrid, Spain.
Abstract
BACKGROUND: Immunotherapy is a promising cancer treatment, but surrogate biomarkers of clinical efficacy have not been fully validated. The aim of this work was to evaluate several biomarkers as predictors of response to nivolumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: Blood samples was collected at baseline, at 2 months after treatment start, and at disease progression. Lactate dehydrogenase level (LDH), neutrophils, and leukocyte values were obtained from medical record. Interleukin (IL)-8, IL-11, and kynurenine/tryptophan levels were determined by enzyme-linked immunosorbent assay. Total protein was extracted from circulating CD8+ T cells, and BCL-2 interacting mediator of cell death (BIM) protein expression tested by western blotting. RESULTS: Baseline LDH levels were significantly higher in non-responder patients than in those who responded (P = .045). The increase in indoleamine 2,3 dioxygenase activity was related to progression of disease, mainly in patients who did not respond to nivolumab treatment (P = .001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (hazard ratio, 7.49; P = .025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. The Student t test and Mann-Whitney U test were used to compare groups for continuous variables. Time to events was estimated using the Kaplan-Meier method, and compared by the log-rank test. CONCLUSIONS: Changes in plasma LDH and IL-8, indoleamine 2,3 dioxygenase activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from nivolumab treatment in these patients.
BACKGROUND: Immunotherapy is a promising cancer treatment, but surrogate biomarkers of clinical efficacy have not been fully validated. The aim of this work was to evaluate several biomarkers as predictors of response to nivolumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: Blood samples was collected at baseline, at 2 months after treatment start, and at disease progression. Lactate dehydrogenase level (LDH), neutrophils, and leukocyte values were obtained from medical record. Interleukin (IL)-8, IL-11, and kynurenine/tryptophan levels were determined by enzyme-linked immunosorbent assay. Total protein was extracted from circulating CD8+ T cells, and BCL-2 interacting mediator of cell death (BIM) protein expression tested by western blotting. RESULTS: Baseline LDH levels were significantly higher in non-responder patients than in those who responded (P = .045). The increase in indoleamine 2,3 dioxygenase activity was related to progression of disease, mainly in patients who did not respond to nivolumab treatment (P = .001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (hazard ratio, 7.49; P = .025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. The Student t test and Mann-Whitney U test were used to compare groups for continuous variables. Time to events was estimated using the Kaplan-Meier method, and compared by the log-rank test. CONCLUSIONS: Changes in plasma LDH and IL-8, indoleamine 2,3 dioxygenase activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from nivolumab treatment in these patients.
Authors: Ana Oitabén; Pablo Fonseca; María J Villanueva; Carme García-Benito; Aida López-López; Alberto Garrido-Fernández; Clara González-Ojea; Laura Juaneda-Magdalena; Martín E Lázaro; Mónica Martínez-Fernández Journal: Cancers (Basel) Date: 2022-05-26 Impact factor: 6.575