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International Journal of Molecular... Mar 2022Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical... (Review)
Review
Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.
Topics: Biomarkers; COVID-19; Humans; Lymphocyte Count; Lymphocytes; Neutrophils; Retrospective Studies
PubMed: 35408994
DOI: 10.3390/ijms23073636 -
Immunity Apr 2022Reinvigoration of exhausted CD8 T (Tex) cells by checkpoint immunotherapy depends on the activation of precursors of exhausted T (Tpex) cells, but the local anatomical...
Reinvigoration of exhausted CD8 T (Tex) cells by checkpoint immunotherapy depends on the activation of precursors of exhausted T (Tpex) cells, but the local anatomical context of their maintenance, differentiation, and interplay with other cells is not well understood. Here, we identified transcriptionally distinct Tpex subpopulations, mapped their differentiation trajectories via transitory cellular states toward Tex cells, and localized these cell states to specific splenic niches. Conventional dendritic cells (cDCs) were critical for successful αPD-L1 therapy and were required to mediate viral control. cDC1s were dispensable for Tpex cell expansion but provided an essential niche to promote Tpex cell maintenance, preventing their overactivation and T-cell-mediated immunopathology. Mechanistically, cDC1s insulated Tpex cells via MHC-I-dependent interactions to prevent their activation within other inflammatory environments that further aggravated their exhaustion. Our findings reveal that cDC1s maintain and safeguard Tpex cells within distinct anatomical niches to balance viral control, exhaustion, and immunopathology.
Topics: CD8-Positive T-Lymphocytes; Cell Differentiation; Dendritic Cells; Immunotherapy; Lymphocyte Count
PubMed: 35366396
DOI: 10.1016/j.immuni.2022.03.006 -
Shock (Augusta, Ga.) Nov 2021
Topics: COVID-19; Humans; Lymphocyte Count; Lymphocytes; Neutrophils; SARS-CoV-2
PubMed: 33337737
DOI: 10.1097/SHK.0000000000001712 -
MMW Fortschritte Der Medizin Nov 2022
Topics: Humans; Pandemics; CD4 Lymphocyte Count; HIV Infections
PubMed: 36376663
DOI: 10.1007/s15006-022-2090-6 -
Thoracic Cancer Nov 2020We evaluated the impact of thoracic radiation in patients with non-small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of...
BACKGROUND
We evaluated the impact of thoracic radiation in patients with non-small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of chemotherapy, and radiation doses in healthy lung tissue.
METHODS
Patients with stage III NSCLC, ECOG 0 to 2, receiving radiotherapy with or without chemotherapy were prospectively evaluated. All patients should be treated with three-dimensional radiotherapy and received biologically effective doses (BED10α/β 10) of 48 to 80 Gy. Peripheral blood lymphocyte total counts were measured at the start of radiotherapy and at 2, 6 and 12 months after radiotherapy. Along with lymphocytes, PTV and doses of 5 Gy and 20 Gy in healthy lung tissue were also evaluated as potential factors influencing overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 46 patients were prospectively evaluated from April 2016 to August 2019, with a median follow-up of 13 months (interquartile range, 1-39 months). The median of OS of all cohort was 22,8 months (IC 95% 17,6-28,1) and the median PFS was 19,5 months (IC 95%: 14,7-24,2). Most patients received concurrent or neoadjuvant chemotherapy (43; 93.4%). No patient received adjuvant immunotherapy. The lower the lymphocyte loss at 6 months after radiotherapy (every 100 lymphocytes/mcL), the greater the chance of PFS (HR, 0.44; 95%CI, 0.25-0.77; P = 0.004) and OS (HR, 0.83; 95%CI, 0.70-0.98; P = 0.025; P = 0.025). BED was a protective factor for both PFS (HR, 0.52; 95%CI 0.33-0.83; P = 0.0006) and OS (HR, 0.73; 95%CI 0.54-0.97; P = 0.029).
CONCLUSIONS
Our results suggest that lymphocyte depletion after radiotherapy reduces tumor control and survival in patients with stage III lung cancer. Radiation doses equal or higher than 60 Gy (BED 72 Gy) improve PFS and OS, but they negatively affect lymphocyte counts for months, which reduces survival and the potential of immunotherapy.
KEY POINTS
SIGNIFICANT FINDINGS OF THE STUDY: Thoracic irradiation for locally advanced lung cancer depletes T lymphocytes for months. Patients whose lymphocyte loss is lower have better overall survival and progression-free survival.
WHAT THIS STUDY ADDS
It is necessary to protect the lymphocyte population, as well as other organs at risk. New forms of irradiation for large fields are needed. Furthermore, could immunotherapy before chemo-radiotherapy, with a greater number of lymphocytes, bring an even better result?
Topics: Female; Humans; Lung Neoplasms; Lymphocyte Count; Male; Middle Aged; Neoplasm Staging; Progression-Free Survival; Prospective Studies
PubMed: 32956564
DOI: 10.1111/1759-7714.13621 -
European Review For Medical and... Sep 2023Acute cholangitis is a serious infectious condition in which systemic complications occur and can lead to mortality. In this study, we tried to elucidate the...
OBJECTIVE
Acute cholangitis is a serious infectious condition in which systemic complications occur and can lead to mortality. In this study, we tried to elucidate the relationship between lymphocyte count and neutrophil-lymphocyte ratio (NLR) with disease severity in patients with acute cholangitis.
PATIENTS AND METHODS
In this retrospective analysis, 633 patients who met the definitive diagnosis criteria for acute cholangitis were enrolled as the study group. In the same period, 155 patients without acute cholangitis who had normal inflammatory markers and underwent endoscopic retrograde cholangiopancreatography (ERCP) were included in the study as the control group. The lymphocyte count, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) of the acute cholangitis group, the control group, and the acute cholangitis group were compared according to the severity of cholangitis.
RESULTS
There was a statistically significant correlation between the severity of cholangitis and the degree of lymphocytopenia (p<0.05). It was observed that as the disease severity increased, the proportion of patients with normal lymphocytopenia degree decreased, and abnormal findings increased. It was seen that the NLR and PLR results of the patients increased as the severity of cholangitis increased.
CONCLUSIONS
As a result, one can conclude that the increase in the severity of cholangitis caused an increase in NLR and PLR and a decrease in lymphocytes. Although the increase in NLR and lymphocytopenia results were considered statistically significant, the increase in PLR was not at an acceptable level.
Topics: Humans; Neutrophils; Retrospective Studies; Platelet Count; Lymphocytes; Lymphocyte Count; Blood Platelets; Cholangitis; Lymphopenia; Prognosis
PubMed: 37782185
DOI: 10.26355/eurrev_202309_33795 -
The Korean Journal of Internal Medicine May 2021Lymphocytes are an important component of the cell-mediated immune system. As lymphopenia is reportedly associated with poor prognoses in patients with various cancers,...
BACKGROUND/AIMS
Lymphocytes are an important component of the cell-mediated immune system. As lymphopenia is reportedly associated with poor prognoses in patients with various cancers, we investigated this notion in patients who underwent curative gastrectomy.
METHODS
We retrospectively analyzed the association between absolute lymphocyte count (ALC) and prognosis in patients with stage I-III gastric cancer who underwent curative surgical resection. Ever lymphopenic patients were defined as those with ALCs < 1,000/μL at any time post-diagnosis except within 30 days post-surgery. Adjusted multivariable regression models were used to evaluate the associations between lymphopenia and overall mortality, gastric cancer-specific mortality, and disease-free survival.
RESULTS
We investigated 1,222 patients diagnosed between January 2011 and December 2015. Fifty-six patients (4.6%) were lymphopenic at diagnosis and nearly one-quarter (24.8%) were ever lymphopenic with a mean minimum ALC of 640/μL. Older age (odds ratio [OR], 1.02) and higher stage (stage III vs. I; OR, 3.01) were positively associated with ever lymphopenia. On multivariable analysis, ever lymphopenia predicted higher overall mortality (hazard ratio [HR], 1.83; p = 0.008), higher gastric cancer-specific mortality (HR, 1.58; p = 0.048), and shorter disease-free survival (HR, 1.83; p = 0.006). The 5-year gastric cancer-specific mortality rates for ever- and never lymphopenic patients were 10.9% and 3.7%, respectively; their 5-year cumulative recurrence rates were 15.1% and 4.6%, respectively.
CONCLUSION
This study demonstrate that ever lymphopenia is independent prognostic factor for overall mortality and recurrence in patients with potentially curable gastric cancer; hence, ALCs may be a biomarker for predicting the prognoses of patients with stage I-III gastric cancer who had curative gastrectomy.
Topics: Aged; Gastrectomy; Humans; Lymphocyte Count; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Stomach Neoplasms
PubMed: 33601866
DOI: 10.3904/kjim.2019.358 -
Scientific Reports Aug 2022The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The... (Observational Study)
Observational Study
The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC < 500 cells/μL) at diagnosis was associated with worse 90-day survival in both types of pneumonia. In POP patients, neutrophilia (ANC > 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.
Topics: Disease Progression; Humans; Lymphocyte Count; Lymphocytes; Lymphopenia; Neutrophils; Pneumonia; Prognosis; Retrospective Studies
PubMed: 36028549
DOI: 10.1038/s41598-022-18794-5 -
World Journal of Gastroenterology Dec 2021Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a dismal 5-year survival rate. PDAC has a complex tumour microenvironment; characterised by... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a dismal 5-year survival rate. PDAC has a complex tumour microenvironment; characterised by a robust desmoplastic stroma, extensive infiltration of immunesuppressive cells such as immature myeloid cells, tumour-associated macrophages, neutrophils and regulatory T cells, and the presence of exhausted and senescent T cells. The cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance, disease progression and spread to distant organs. PDAC tumours, considered to be non-immunogenic or cold, express low mutation burden, low infiltration of CD8 cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue, and often display an exhausted phenotype. Here, we review the role of T cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.
Topics: Carcinoma, Pancreatic Ductal; Humans; Lymphocyte Count; Pancreas; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 35046623
DOI: 10.3748/wjg.v27.i46.7956 -
Arthritis Care & Research Mar 2023To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease...
OBJECTIVE
To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc).
METHODS
Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality.
RESULTS
Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P < 0.001 and b = 2.32, P < 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P = 0.02 and HR 1.48, P < 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II.
CONCLUSION
Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc.
Topics: Humans; Neutrophils; Lymphocytes; Scleroderma, Systemic; Disease Progression; Skin; Lymphocyte Count
PubMed: 35287250
DOI: 10.1002/acr.24880