Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer
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-...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00125/full |
| _version_ | 1811289649812865024 |
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| author | Selene Ottonello Carlo Genova Irene Cossu Vincenzo Fontana Erika Rijavec Giovanni Rossi Giovanni Rossi Federica Biello Maria Giovanna Dal Bello Marco Tagliamento Angela Alama Simona Coco Simona Boccardo Irene Vanni Guido Ferlazzo Guido Ferlazzo Guido Ferlazzo Lorenzo Moretta Francesco Grossi Maria Cristina Mingari Maria Cristina Mingari Paolo Carrega Paolo Carrega Gabriella Pietra Gabriella Pietra |
| author_facet | Selene Ottonello Carlo Genova Irene Cossu Vincenzo Fontana Erika Rijavec Giovanni Rossi Giovanni Rossi Federica Biello Maria Giovanna Dal Bello Marco Tagliamento Angela Alama Simona Coco Simona Boccardo Irene Vanni Guido Ferlazzo Guido Ferlazzo Guido Ferlazzo Lorenzo Moretta Francesco Grossi Maria Cristina Mingari Maria Cristina Mingari Paolo Carrega Paolo Carrega Gabriella Pietra Gabriella Pietra |
| author_sort | Selene Ottonello |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T03:58:05Z |
| format | Article |
| id | doaj.art-d2bc4156441047f087b7ab4cc39af254 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T03:58:05Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d2bc4156441047f087b7ab4cc39af2542022-12-22T03:03:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00125483189Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung CancerSelene Ottonello0Carlo Genova1Irene Cossu2Vincenzo Fontana3Erika Rijavec4Giovanni Rossi5Giovanni Rossi6Federica Biello7Maria Giovanna Dal Bello8Marco Tagliamento9Angela Alama10Simona Coco11Simona Boccardo12Irene Vanni13Guido Ferlazzo14Guido Ferlazzo15Guido Ferlazzo16Lorenzo Moretta17Francesco Grossi18Maria Cristina Mingari19Maria Cristina Mingari20Paolo Carrega21Paolo Carrega22Gabriella Pietra23Gabriella Pietra24Department of Experimental Medicine (DiMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyCenter for Autoinflammatory Diseases and Immunodeficiencies - Pediatric Clinic and Rheumatology, Giannina Gaslini Institute, Genoa, ItalyClinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMedical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLaboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, ItalyDivision of Clinical Pathology, University Hospital Policlinico G. Martino, Messina, ItalyCell Factory Center, University of Messina, Messina, Italy0Department of Immunology, IRCCS Bambino Gesù Children's Hospital, Rome, ItalyMedical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Experimental Medicine (DiMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy1Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyLaboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, ItalyCell Factory Center, University of Messina, Messina, ItalyDepartment of Experimental Medicine (DiMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy1Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyImmune 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.00125/fullnivolumabPD-1biomarkersnon-small-cell lung cancerperipheral bloodimmune checkpoint |
| spellingShingle | Selene Ottonello Carlo Genova Irene Cossu Vincenzo Fontana Erika Rijavec Giovanni Rossi Giovanni Rossi Federica Biello Maria Giovanna Dal Bello Marco Tagliamento Angela Alama Simona Coco Simona Boccardo Irene Vanni Guido Ferlazzo Guido Ferlazzo Guido Ferlazzo Lorenzo Moretta Francesco Grossi Maria Cristina Mingari Maria Cristina Mingari Paolo Carrega Paolo Carrega Gabriella Pietra Gabriella Pietra Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer Frontiers in Immunology nivolumab PD-1 biomarkers non-small-cell lung cancer peripheral blood immune checkpoint |
| title | Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer |
| title_full | Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer |
| title_fullStr | Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer |
| title_full_unstemmed | Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer |
| title_short | Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer |
| title_sort | association between response to nivolumab treatment and peripheral blood lymphocyte subsets in patients with non small cell lung cancer |
| topic | nivolumab PD-1 biomarkers non-small-cell lung cancer peripheral blood immune checkpoint |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00125/full |
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