M Charrier1, L Mezquita2, B Lueza3, L Dupraz4, D Planchard5, J Remon5, C Caramella6, L Cassard4, L Boselli4, K S Reiners7, E Pogge von Strandmann8, S Rusakiewicz9, R Ferrara4, B Duchemann1, M Naigeon1, J P Pignon3, B Besse10, N Chaput11. 1. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; University Paris-Saclay, Faculty of Medicine, F-94270, Le Kremlin-Bicêtre, France. 2. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Department of Cancer Medicine, Gustave Roussy Cancer Campus, F-94805, Villejuif, France. 3. Biostatistics and Epidemiology Department, University Paris Saclay, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Oncostat CESP, INSERM, University Paris-Saclay, France; UVSQ, University Paris-Sud, F-94085, Villejuif, France. 4. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France. 5. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Department of Cancer Medicine, Gustave Roussy Cancer Campus, F-94805, Villejuif, France. 6. Radiology Department, Gustave Roussy, Cancer Campus, F-94085, Villejuif, France. 7. Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, Germany. 8. Experimental Tumor Research, Center for Tumor Biology and Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University, 35043 Marburg, Germany. 9. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France. 10. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; University Paris-Saclay, Faculty of Medicine, F-94270, Le Kremlin-Bicêtre, France; Department of Cancer Medicine, Gustave Roussy Cancer Campus, F-94805, Villejuif, France. 11. Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; University Paris-Saclay, Faculty of Pharmacy, Chatenay-Malabry, F-92296, France. Electronic address: nathalie.chaput@gustaveroussy.fr.
Abstract
INTRODUCTION: Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed. METHODS: Advanced treatment-naive non-small cell lung cancer (NSCLC) patients eligible for first-line platinum-based chemotherapy were prospectively included from December 2012 to July 2015 (N = 148). Blood samples of patients were collected before the first cycle for fresh NK cell phenotyping. Peripheral blood mononuclear cells were cryopreserved for natural cytotoxicity receptor (NCR) genotyping as well as sera for NCR's ligand quantification. Data on leukocytes, neutrophils and monocyte counts and lactate dehydrogenase (LDH) levels were extracted from electronic medical records. RESULTS: Among all studied markers, monocytosis, neutrophilia, leucocytosis, high LDH and sBAG6 levels and reduced levels of NCR3 transcripts were associated with poor overall survival (OS) in univariate analysis. The levels of NCR3 transcripts was linked to age, number of metastatic sites, monocyte counts, LDH and sBAG6 levels. Neutrophilia was associated to high sBAG6 levels. NCR3 was the unique innate immune parameter that remained as an independent factor associated with both OS (P = 0.003) and progression-free survival (P = 0.009) in the multivariate analysis. CONCLUSION: This study brought evidence that these biomarkers are entangled; parameters associated with an inflammatory process were related to reduced levels of NCR3 transcripts. Finally, the level of NCR3 transcripts was independently associated with outcomes in treatment-naive patients with advanced NSCLC.
INTRODUCTION: Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed. METHODS: Advanced treatment-naive non-small cell lung cancer (NSCLC) patients eligible for first-line platinum-based chemotherapy were prospectively included from December 2012 to July 2015 (N = 148). Blood samples of patients were collected before the first cycle for fresh NK cell phenotyping. Peripheral blood mononuclear cells were cryopreserved for natural cytotoxicity receptor (NCR) genotyping as well as sera for NCR's ligand quantification. Data on leukocytes, neutrophils and monocyte counts and lactate dehydrogenase (LDH) levels were extracted from electronic medical records. RESULTS: Among all studied markers, monocytosis, neutrophilia, leucocytosis, high LDH and sBAG6 levels and reduced levels of NCR3 transcripts were associated with poor overall survival (OS) in univariate analysis. The levels of NCR3 transcripts was linked to age, number of metastatic sites, monocyte counts, LDH and sBAG6 levels. Neutrophilia was associated to high sBAG6 levels. NCR3 was the unique innate immune parameter that remained as an independent factor associated with both OS (P = 0.003) and progression-free survival (P = 0.009) in the multivariate analysis. CONCLUSION: This study brought evidence that these biomarkers are entangled; parameters associated with an inflammatory process were related to reduced levels of NCR3 transcripts. Finally, the level of NCR3 transcripts was independently associated with outcomes in treatment-naive patients with advanced NSCLC.
Authors: Boris Duchemann; Jordi Remon; Marie Naigeon; Lydie Cassard; Jean Mehdi Jouniaux; Lisa Boselli; Jonathan Grivel; Edouard Auclin; Aude Desnoyer; Benjamin Besse; Nathalie Chaput Journal: Transl Lung Cancer Res Date: 2021-06