Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer

Frontiers in Immunology

Lorenzo Moretta¹  Gabriella Pietra²  Maria Cristina Mingari²  Guido Ferlazzo³  Paolo Carrega³  Irene Cossu⁴  Vincenzo Fontana⁵  Selene Ottonello⁶  Giovanni Rossi⁷  Angela Alama^1,10  Simona Coco^1,10  Maria Giovanna Dal Bello^1,10  Marco Tagliamento^1,10  Irene Vanni^1,10  Federica Biello^1,10  Simona Boccardo^1,10  Carlo Genova^1,10  Erika Rijavec^1,11  Francesco Grossi^1,11 

[1] 0Department of Immunology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy;1Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;Cell Factory Center, University of Messina, Messina, Italy;Center for Autoinflammatory Diseases and Immunodeficiencies - Pediatric Clinic and Rheumatology, Giannina Gaslini Institute, Genoa, Italy;Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;Department of Experimental Medicine (DiMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy;Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy;Division of Clinical Pathology, University Hospital Policlinico G. Martino, Messina, Italy;Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy;Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy;

关键词: nivolumab;    PD-1;    biomarkers;    non-small-cell lung cancer;    peripheral blood;    immune checkpoint;   

DOI  :  10.3389/fimmu.2020.00125

来源: DOAJ

【 摘 要 】

Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients (n = 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3+, CD4+, and CD8+ T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3+ and CD8+ T cells (p = 0.013 and p = 0.033, respectively). The pre-treatment level of exhausted T cells (CD8+PD1+Eomes+) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) (p = 0.046). In CD patients, the frequency of exhausted CD8+ T cells further decreased during treatment cycles (p = <0.0001, p = 0.0032, and p = 0.0239, respectively). In conclusion, our results suggest that the distribution of lymphocyte subsets and expression of PD-1 on T cells before treatment may help predict the outcome of anti-PD-1 treatment in NSCLC patients. In addition, assessing the initial levels of exhausted T cells as well as their decrease upon treatment may also predict response and clinical outcome.

【 授权许可】

Unknown