Frontiers in immunology
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Frontiers in immunology · Jan 2020
Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19).
Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. ⋯ Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
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Frontiers in immunology · Jan 2020
Prenatal Maternal Stress Causes Preterm Birth and Affects Neonatal Adaptive Immunity in Mice.
Maternal stress is a well-established risk factor for preterm birth and has been associated with adverse neonatal outcomes in the first and subsequent generations, including increased susceptibility to disease and lasting immunological changes. However, a causal link between prenatal maternal stress and preterm birth, as well as compromised neonatal immunity, has yet to be established. To fill this gap in knowledge, we used a murine model of prenatal maternal stress across three generations and high-dimensional flow cytometry to evaluate neonatal adaptive immunity. ⋯ Yet, neonatal adaptive immunity gained resilience against prenatal maternal stress by the third generation. We also show that the rate of prenatal maternal stress-induced preterm birth can be reduced upon cessation of stress, though neonatal growth impairments persisted. These findings provide evidence that prenatal maternal stress causes preterm birth and affects neonatal immunity across generations, adverse effects that can be ameliorated upon cessation.
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Frontiers in immunology · Jan 2020
Identification of Unique mRNA and miRNA Expression Patterns in Bone Marrow Hematopoietic Stem and Progenitor Cells After Trauma in Older Adults.
Older adults have significantly worse morbidity and mortality after severe trauma than younger cohorts. The competency of the innate immune response decreases with advancing age, especially after an inflammatory insult. Subsequent poor outcomes after trauma are caused in part by dysfunctional leukocytes derived from the host's hematopoietic stem and progenitor cells (HSPCs). ⋯ These differences could potentially explain why older adult patients have a suboptimal hematopoietic response to trauma. Although immunomodulation of HSPCs may be a necessary consideration to promote host protective immunity after host injury, the age related differences further highlight that patients may require an age-defined medical approach with interventions that are specific to their transcriptomic and biologic response. Also, targeting the older adult miRs may be possible for interventions in this patient population.
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Frontiers in immunology · Jan 2020
PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients.
The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies. ⋯ Our data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment.
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Frontiers in immunology · Jan 2020
Observational StudyDynamics of Serum Tumor Markers Can Serve as a Prognostic Biomarker for Chinese Advanced Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors.
Background: Serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cytokeratin 19 fragment (CYFRA21-1) and squamous-cell carcinoma-related antigen (SCC-Ag) are routinely used for monitoring the response to chemotherapy or targeted therapy in advanced-stage non-small cell lung cancer (NSCLC), however their role in immunotherapy remains unclear. The aim of this study was to investigate whether dynamics of these serum markers were associated with the efficacy and prognosis of Chinese late-stage NSCLC patients treated with programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors. Methods: We initiated a longitudinal prospective study on advanced NSCLC patients treated with PD-1/PD-L1 inhibitors in Chinese PLA general hospital (Beijing, China). ⋯ So as in patients with squamous cell carcinoma, meaningful improvements in at least 2 out of 4 biomarkers were linked to better ORR (0.42 vs. 0.08, p = 0.014), longer PFS (median: 13.1 vs. 5.6 months, p = 0.001), and OS (median: 25.6 vs. 10.9 months, p = 0.06). Conclusions: The dynamic change of CEA, CA125, CYFRA21-1, and SCC-Ag from baseline have prognostic value for late-stage NSCLC patients treated with PD-1/PD-L1 inhibitors. Decrease of associated biomarkers serum levels were associated with favorable clinical outcomes.