Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia DOI Creative Commons
Lara Gibellini, Sara De Biasi, Annamaria Paolini

и другие.

EMBO Molecular Medicine, Год журнала: 2020, Номер 12(12)

Опубликована: Окт. 20, 2020

In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood from with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics mitochondrial dysfunction, had reduced basal maximal respiration, spare respiratory capacity, decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting capability perform aerobic glycolysis. Although ability oxidative burst, they were still capable producing TNF IFN-γ in vitro. A significantly high amount depolarized mitochondria abnormal ultrastructure. redistribution monocyte subsets, significant expansion intermediate/pro-inflammatory cells, amounts immature found, along concomitant compression classical monocytes, increased expression inhibitory checkpoints like PD-1/PD-L1. High plasma levels several inflammatory cytokines chemokines, including GM-CSF, IL-18, CCL2, CXCL10, osteopontin, finally confirm the importance immunopathogenesis.

Язык: Английский

Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer DOI
Nina G. Steele, Eileen S. Carpenter, Samantha B. Kemp

и другие.

Nature Cancer, Год журнала: 2020, Номер 1(11), С. 1097 - 1112

Опубликована: Окт. 26, 2020

Язык: Английский

Процитировано

373
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma DOI Creative Commons
David A. Braun, Kelly Street, Kelly P. Burke

и другие.

Cancer Cell, Год журнала: 2021, Номер 39(5), С. 632 - 648.e8

Опубликована: Март 12, 2021

Язык: Английский

Процитировано

351
Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy DOI Creative Commons
Shiping Jiao, Sumit K. Subudhi, Ana M. Aparicio

и другие.

Cell, Год журнала: 2019, Номер 179(5), С. 1177 - 1190.e13

Опубликована: Ноя. 1, 2019

Язык: Английский

Процитировано

338
muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data DOI Creative Commons
Helena L. Crowell, Charlotte Soneson, Pierre‐Luc Germain

и другие.

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Ноя. 30, 2020

Single-cell RNA sequencing (scRNA-seq) has become an empowering technology to profile the transcriptomes of individual cells on a large scale. Early analyses differential expression have aimed at identifying differences between subpopulations identify subpopulation markers. More generally, such methods compare levels across sets cells, thus leading cross-condition analyses. Given emergence replicated multi-condition scRNA-seq datasets, area increasing focus is making sample-level inferences, termed here as state analysis; however, it not clear which statistical framework best handles this situation. Here, we surveyed perform analyses, including cell-level mixed models and based aggregated pseudobulk data. To evaluate method performance, developed flexible simulation that mimics multi-sample We analyzed data from mouse cortex uncover subpopulation-specific responses lipopolysaccharide treatment, provide robust tools for analysis within muscat R package.

Язык: Английский

Процитировано

330
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) DOI Creative Commons
Andrea Cossarizza, Hyun‐Dong Chang, Andreas Radbruch

и другие.

European Journal of Immunology, Год журнала: 2021, Номер 51(12), С. 2708 - 3145

Опубликована: Дек. 1, 2021

Abstract The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes functional assays all major human murine immune cell subsets. Notably, contain helpful tables highlighting differences between cells. Another useful feature this is analysis clinical samples with examples applications in context autoimmune diseases, cancers as well acute chronic infectious diseases. Furthermore, there are detailing tips, tricks pitfalls avoid. All written peer‐reviewed by leading experts immunologists, making an essential state‐of‐the‐art handbook for basic researchers.

Язык: Английский

Процитировано

324
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity DOI Creative Commons
David Ahern, Zhichao Ai, Mark Ainsworth

и другие.

Cell, Год журнала: 2022, Номер 185(5), С. 916 - 938.e58

Опубликована: Янв. 21, 2022

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire, acute phase response, metabolism, coagulation. Persisting activation involving AP-1/p38MAPK was feature COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive outcome. Systems-based integrative analyses tensor matrix decomposition all modalities revealed groupings linked specificity compared to sepsis. Our approach will support future drug development, trial design, personalized medicine approaches

Язык: Английский

Процитировано

272
Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma DOI
Jianjun Gao, Neema Navai, Omar Alhalabi

и другие.

Nature Medicine, Год журнала: 2020, Номер 26(12), С. 1845 - 1851

Опубликована: Окт. 12, 2020

Язык: Английский

Процитировано

266
Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes DOI Creative Commons
Maha K. Rahim, Trine Line Hauge Okholm, Kyle B. Jones

и другие.

Cell, Год журнала: 2023, Номер 186(6), С. 1127 - 1143.e18

Опубликована: Март 1, 2023

CD8

Язык: Английский

Процитировано

238
Neoadjuvant relatlimab and nivolumab in resectable melanoma DOI Creative Commons
Rodabe N. Amaria, Michael A. Postow, Elizabeth M. Burton

и другие.

Nature, Год журнала: 2022, Номер 611(7934), С. 155 - 160

Опубликована: Окт. 26, 2022

Abstract Relatlimab and nivolumab combination immunotherapy improves progression-free survival over monotherapy in patients with unresectable advanced melanoma 1 . We investigated this regimen resectable clinical stage III or oligometastatic IV (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg relatlimab 160 intravenously every 4 weeks) followed by surgery, then ten of adjuvant therapy. The primary end point was pathologic complete response (pCR) rate 2 resulted 57% pCR 70% overall among 30 treated. radiographic using Response Evaluation Criteria Solid Tumors 1.1 57%. No grade 3–4 immune-related adverse events were observed the setting. 1- 2-year recurrence-free 100% 92% for any response, compared to 88% 55% who did not have a ( P = 0.005). Increased immune cell infiltration at baseline, decrease M2 macrophages during treatment, associated response. Our results indicate that induces high rate. Safety therapy is favourable other regimens. These data, RELATIVITY-047 trial , provide further confirmation efficacy safety new regimen.

Язык: Английский

Процитировано

236
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma DOI Creative Commons

Giulia Agliardi,

Anna Rita Liuzzi,

Alastair Hotblack

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Янв. 19, 2021

Abstract Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with single, locally delivered dose IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity cells, also reshapes TME, driving increased infiltration proinflammatory CD4 + T decreased numbers regulatory (Treg), activation myeloid compartment. Importantly, immunotherapy-enabling benefits achieved minimal systemic effects. Our findings thus local delivery may be adjuvant cell therapy GBM.

Язык: Английский

Процитировано

218