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A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience.
Watanabe, J, Saito, M, Horimoto, Y, Nakamoto, S
Breast cancer research and treatment. 2020;(1):211-220
Abstract
PURPOSE Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement. METHODS HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed. RESULTS A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/μL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/μL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers. CONCLUSION In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.
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High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study.
Miyoshi, Y, Yoshimura, Y, Saito, K, Muramoto, K, Sugawara, M, Alexis, K, Nomoto, K, Nakamura, S, Saeki, T, Watanabe, J, et al
Breast cancer (Tokyo, Japan). 2020;(4):706-715
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BACKGROUND Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS). METHODS The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively. RESULTS Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin. DISCUSSION This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures. TRIAL REGISTRATION www.ClinicalTrials.gov code: NCT00388726.
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Desensitization to chemical and food sensitivities by low-dose immunotherapy ascertained by provocation neutralization is associated with reduced influx of calcium ions into lymphocytes.
Puri, BK, Howard, JM, Monro, JA
Journal of complementary & integrative medicine. 2017;(2)
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Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23 % for metabisulfite sensitivity (p<0.0004); 12 % for salicylate sensitivity (p<0.01); 23 % for benzoate sensitivity (p<0.01); 30 % for formaldehyde sensitivity (p<0.0001); 16 % for sensitivity to petrol exhaust (p<0.003); 16 % for natural gas sensitivity (p<0.001); 13 % for nickel sensitivity (p<0.05); 30 % for sensitivity to organophosphates (p<0.01); and 24 % for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.
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Distributional and functional alterations of immunocompetent peripheral blood lymphocytes in patients with chronic pancreatitis.
Gansauge, F, Gansauge, S, Eh, M, Schlosser, W, Ramadani, M, Kern, P, Beger, HG
Annals of surgery. 2001;(3):365-70
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OBJECTIVE To investigate whether the chronic inflammatory process in patients with chronic pancreatitis affects their immune function. SUMMARY BACKGROUND DATA Chronic pancreatitis is a chronic inflammatory disease of the exocrine pancreas. In approximately 30% of patients, an inflammatory mass of the pancreatic head is found, representing an indication for surgery. METHODS This study comprised 28 patients with chronic pancreatitis. Sixteen patients were also reevaluated 1 year after resection of the pancreatic head for chronic pancreatitis. RESULTS Compared with an age- and gender-matched control group, the number of CD3(+) cells was significantly increased in patients with chronic pancreatitis, with an increase of both CD3(+)CD4(+) and CD3(+)CD8(+) cells. The number of natural killer cells or B lymphocytes did not differ between the patients and the control group. After stimulation with phytohemagglutinin or anti-CD3 antibodies, the blastogenic response was significantly attenuated in the patients with chronic pancreatitis. One year after resection of the pancreatic head for chronic pancreatitis, the distribution and the blastogenic response to phytohemagglutinin and anti-CD3 antibodies had returned to normal compared with preoperative values. CONCLUSION The chronic inflammatory process in chronic pancreatitis markedly affects the distribution and function of peripheral immunocompetent blood cells, and elimination of the chronic inflammatory focus by pancreatic head resection restores the suppressed immune function in these patients.
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[Expression of adhesion molecules LFA-1 (CD11a and ICAM-1 (CD54) on lymphocytes and chemokines IL-8 and MCP-1 concentrations in bronchoalveolar lavage of patients with asthma or chronic obstructive pulmonary disease].
Jahnz-Rózyk, K, Chciałowski, A, Pirozyńska, E, Rogalewska, A
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2000;(52):649-52
Abstract
Chemokines and cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues asthma and chronic obstructive pulmonary disease (COPD) are a complex of conditions, which have airflow limitation in common. The aim of this study was to determine the numbers and percentages of lymphocytes expressing adhesion molecules: LFA-1, ICAM-1 together with assessment of chemokines concentrations: IL-8 and MCP-1 in bronchoalveolar lavage fluid (BAL) of patients with asthma or chronic obstructive pulmonary disease (COPD). 12 patients with asthma, 14 patients with COPD, and 6 subjects of control group took part in this study. The expression of LFA-1 and ICAM-1 was assessed on lymphocytes by using immunohistochemistry (streptavidyn-biotin, DAKO, Denmark). ELISA test was used to measure IL-8 and MCP-1 concentrations in BAL (kits from R&D, USA). The percentage of lymphocytes expressing LFA-1 and ICAM-1 were: 33.9 +/- 23.8% and 25.8 +/- 12.2% in COPD patients, 23.9 +/- 12.1% and 15.3 +/- 4.42% in asthma patients, and 14.2 +/- 10% and 5.2 +/- 1.6% in the control group respectively. There was observed significant difference between the percentage of lymphocytes expressing LFA-1 and ICAM-1 of COPD and the control group. The concentrations of IL-8 were: 2306 +/- 1501 pg/ml in COPD, 233 +/- 27.3 pg/ml in asthma and 64 +/- 28.7 in the control group (p < 0.05). The concentrations of MCP-1 were: 768.9 +/- 668.1 pg/ml in COPD, 126.8 +/- 30.8 pg/ml in asthma, and 83.0 +/- 16.4 pg/ml in the control group (p < 0.05). There was observed correlation between lymphocytes expressing LFA-1 and IL-8 concentration (r = +0.5, p < 0.05) and between lymphocytes expressing LFA-1 and MCP-1 concentration (r = +0.5, p < 0.05), and between lymphocytes expressing ICAM-1 and MCP-1 concentration (r = +0.4, p < 0.05) only in COPD patients. Our data suggest that LFA-1 and ICAM-1 are important molecules in the recruitment of leukocytes and together with IL-8 and MCP-1 may have a role in pathomechanism of inflammation in asthma and especially in COPD.