The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Angela Alama - One of the best experts on this subject based on the ideXlab platform.
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association between response to nivolumab treatment and Peripheral Blood Lymphocyte subsets in patients with non small cell lung cancer
Frontiers in Immunology, 2020Co-Authors: Selene Ottonello, Carlo Genova, Irene Cossu, Vincenzo Fontana, Erika Rijavec, Giovanni A Rossi, Federica Biello, Maria Giovanna Dal Bello, Marco Tagliamento, Angela AlamaAbstract: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.
Selene Ottonello - One of the best experts on this subject based on the ideXlab platform.
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association between response to nivolumab treatment and Peripheral Blood Lymphocyte subsets in patients with non small cell lung cancer
Frontiers in Immunology, 2020Co-Authors: Selene Ottonello, Carlo Genova, Irene Cossu, Vincenzo Fontana, Erika Rijavec, Giovanni A Rossi, Federica Biello, Maria Giovanna Dal Bello, Marco Tagliamento, Angela AlamaAbstract: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.
Thomas J Kakuk - One of the best experts on this subject based on the ideXlab platform.
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tirilazad mesylate effects of the 21 aminosteroid on the lymphoid system of laboratory animals a comparison with the glucocorticoid methylprednisolone
Toxicological Sciences, 1995Co-Authors: Terry A Jackson, Ricardo Ochoa, Thomas J KakukAbstract:Abstract Tirilazad Mesylate—Effects of the 21-Aminosteroid on the Lymphoid System of Laboratory Animals: A Comparison with the Glucocorticoid Methylprednisolone. Jackson, T. A., Ochoa, R., and Kakuk, T. J. (1995). Fundam. Appl. Toxicol. 26, 246-257. Four-week toxicity studies with the 21-aminosteroid tirilazad mesylate were conducted in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys to support development of the drug for use in various clinical syndromes of injury to the central nervous system of humans. As the immune system is involved in many of the obvious side effects of glucocorticoids used currently for this indication, particular attention was directed to the lymphoid system; results were contrasted with similar data from studies with methylprednisolone, a classical glucocorticoid. Administration of tirilazad mesylate to rats, dogs and monkeys for 4 weeks had no effects at the highest doses tested on parameters assessed, including absolute Peripheral Blood Lymphocyte counts, thymus or adrenal weights, circulating levels of cortisol, or Lymphocyte proliferation response to phytohemagglutinin-P. Germinal centers in lymphoid tissues from dogs given high doses of tirilazad contained small numbers of macrophages with vacuolated cytoplasm but no other changes; lymphoid tissues in rats and monkeys given tirilazad were morphologically normal. Administration of methylprednisolone for a similar duration in rats and dogs at high dose levels was associated with increased death rates due to bacterial infections, markedly decreased Peripheral Blood Lymphocyte counts and weights of thymus and adrenal glands, and prominent lymphoid atrophy as well as decreased circulating levels of cortisol. Female dogs infused for 10 days with a high dose of methylprednisolone had depression of the in vitro proliferation response of Peripheral Blood Lymphocytes to phytohemagglutinin-P.
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Tirilazad Mesylate—Effects of the 21-Aminosteroid on the Lymphoid System of Laboratory Animals: A Comparison with the Glucocorticoid Methylprednisolone
Toxicological Sciences, 1995Co-Authors: Terry A Jackson, Ricardo Ochoa, Thomas J KakukAbstract:Abstract Tirilazad Mesylate—Effects of the 21-Aminosteroid on the Lymphoid System of Laboratory Animals: A Comparison with the Glucocorticoid Methylprednisolone. Jackson, T. A., Ochoa, R., and Kakuk, T. J. (1995). Fundam. Appl. Toxicol. 26, 246-257. Four-week toxicity studies with the 21-aminosteroid tirilazad mesylate were conducted in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys to support development of the drug for use in various clinical syndromes of injury to the central nervous system of humans. As the immune system is involved in many of the obvious side effects of glucocorticoids used currently for this indication, particular attention was directed to the lymphoid system; results were contrasted with similar data from studies with methylprednisolone, a classical glucocorticoid. Administration of tirilazad mesylate to rats, dogs and monkeys for 4 weeks had no effects at the highest doses tested on parameters assessed, including absolute Peripheral Blood Lymphocyte counts, thymus or adrenal weights, circulating levels of cortisol, or Lymphocyte proliferation response to phytohemagglutinin-P. Germinal centers in lymphoid tissues from dogs given high doses of tirilazad contained small numbers of macrophages with vacuolated cytoplasm but no other changes; lymphoid tissues in rats and monkeys given tirilazad were morphologically normal. Administration of methylprednisolone for a similar duration in rats and dogs at high dose levels was associated with increased death rates due to bacterial infections, markedly decreased Peripheral Blood Lymphocyte counts and weights of thymus and adrenal glands, and prominent lymphoid atrophy as well as decreased circulating levels of cortisol. Female dogs infused for 10 days with a high dose of methylprednisolone had depression of the in vitro proliferation response of Peripheral Blood Lymphocytes to phytohemagglutinin-P.
Neil L Berinstein - One of the best experts on this subject based on the ideXlab platform.
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a short course of neoadjuvant irx 2 induces changes in Peripheral Blood Lymphocyte subsets of patients with head and neck squamous cell carcinoma
Cancer Immunology Immunotherapy, 2012Co-Authors: Theresa L Whiteside, Lisa H Butterfield, Paul H Naylor, James E Egan, John W Hadden, Lorraine Baltzer, Gregory T Wolf, Neil L BerinsteinAbstract:Objective IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased Lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10 days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, Peripheral Blood Lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2.
Carlo Genova - One of the best experts on this subject based on the ideXlab platform.
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association between response to nivolumab treatment and Peripheral Blood Lymphocyte subsets in patients with non small cell lung cancer
Frontiers in Immunology, 2020Co-Authors: Selene Ottonello, Carlo Genova, Irene Cossu, Vincenzo Fontana, Erika Rijavec, Giovanni A Rossi, Federica Biello, Maria Giovanna Dal Bello, Marco Tagliamento, Angela AlamaAbstract: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.