Dataset Information

Early Expression of Functional Markers on CD4⁺ T Cells Predicts Outcomes in ICU Patients With Sepsis.

ABSTRACT:

Objective

There is evidence that metabolic disorder, dysfunction and abnormal apoptosis of immune cells are closely related to immunosuppression in sepsis. Single monitoring of exhaustion receptors does not reflect well the immune status of septic patients; therefore, we monitored immune status in relation to metabolism, function and apoptosis of immune cells to find good prognostic indicators for sepsis.

Design

A single-center prospective observational study.

Setting

Teaching hospital including an academic tertiary care center.

Patients

81 patients with sepsis and 22 without sepsis admitted to the ICU.

Interventions

Patients were divided according to Sequential Organ Failure Assessment (SOFA) score: mild sepsis 2-5 points and severe sepsis ≥6 points. SOFA score was recalculated daily. If it changed by ≥2 points within 2 days, T-cell metabolism, function and apoptotic makers [mammalian target of rapamycin (mTOR), T-bet, interferon (IFN)-γ, granzyme B, and programmed cell death (PD)-1] were continuously monitored on days 1, 3 and 5 after admission.

Measurements and main results

The overall status of immune cells was compared among patients with different severity of sepsis. Patients with severe sepsis, compared with mild and no sepsis, had lower lymphocyte counts, higher expression of receptors associated with cell metabolism, activation and apoptosis, and lower expression of functional receptors. Multivariate regression analysis revealed that frequency of CD4⁺ T cells expressing mTOR, IFN-γ and PD-1 at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that frequency of CD4⁺ T cells expressing mTOR, IFN-γ and PD-1 predicted 28-day mortality, with cutoffs of 30.57%, 12.81% and 22.46%, respectively. The expression of related receptors on CD8+ T cells showed similar trend to that on CD4+ T cells, but no significant difference was found.

Conclusions

Abnormally increased expression of metabolic and apoptotic receptors on CD4⁺ T cells and decreased expression of functional factors are associated with poor prognosis in ICU patients with sepsis. Poor prognosis can be identified by early detection of expression of mammalian target of rapamycin (mTOR), IFN-γ and PD-1 on CD4⁺ T cells.

SUBMITTER: Chen J

PROVIDER: S-EPMC9309518 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Perioperative immune checkpoint inhibitors have been shown to improve prognosis in early-stage lung cancer. However, no biomarkers are known to indicate the requirement for treatment. This study aimed to identify T-cell clusters responsible for antitumor immunity in patients with early-stage lung cancer. Preoperative blood samples from 50 consecutive patients with lung cancer who were diagnosed as operable and underwent complete resection were analyzed by mass cytometry. Patients were divided into two groups: no recurrence at a minimum observation period of 851 days (median observation period: 1,031.5 days) and recurrence by the last observation date. Mass cytometry and single-cell RNA sequencing analysis of lymph nodes (LN) and tumor-infiltrating T cells were also performed. CCR4-CCR6+ Th7R showed discriminative ability between recurrence and non-recurrence patients with lung cancer. Patients with more than 3.04% Th7R showed significantly favorable disease-free survival. Th7R was a major component of CD4+ T cells in tumor microenvironments and LNs adjacent to lung cancer tissues and was the only cluster that decreased in peripheral blood after the removal of cancer tissues, suggesting that Th7R was primed and proliferated in tumor-draining LNs in the presence of cancer tissues. Th7R had the kinetics that antitumor T cells should have, as indicated by the cancer immunity cycle; thus, peripheral blood Th7R could represent the potency of tumor immunity by reflecting priming and proliferation in tumor-draining LNs and Th7R in the tumor microenvironment. Prediction using peripheral Th7R before surgery could allow the selection of patients who require perioperative drug therapy and optimize therapeutic interventions with clinical implications.SignificancePeripheral Th7R, a Th1-like CD4+ T-cell cluster reflecting priming status in draining LNs and immune status in the tumor microenvironment, predicts disease-free survival after complete resection and has significant clinical relevance in selecting appropriate therapeutic interventions in patients with early-stage lung cancer.

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Dataset Information

Early Expression of Functional Markers on CD4⁺ T Cells Predicts Outcomes in ICU Patients With Sepsis.

Objective

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Early Expression of Functional Markers on CD4+ T Cells Predicts Outcomes in ICU Patients With Sepsis.

Objective

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Early Expression of Functional Markers on CD4⁺ T Cells Predicts Outcomes in ICU Patients With Sepsis.