Introduction to systems immunology and infection microbiology

AbstractThe emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

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Immunological Genome Project and systems immunology

Trends in Immunology ◽

10.1016/j.it.2013.03.004 ◽

2013 ◽

Vol 34 (12) ◽

pp. 602-609 ◽

Cited By ~ 96

Author(s):

Tal Shay ◽

Joonsoo Kang

Keyword(s):

Genome Project ◽

Systems Immunology

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Human systems immunology: Hypothesis-based modeling and unbiased data-driven approaches

Seminars in Immunology ◽

10.1016/j.smim.2012.11.003 ◽

2013 ◽

Vol 25 (3) ◽

pp. 193-200 ◽

Cited By ~ 22

Author(s):

Arnon Arazi ◽

William F. Pendergraft ◽

Ruy M. Ribeiro ◽

Alan S. Perelson ◽

Nir Hacohen

Keyword(s):

Data Driven ◽

Systems Immunology ◽

Human Systems

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Parasite species regulates T cell activation in human malaria

10.1101/2021.03.22.21252810 ◽

2021 ◽

Author(s):

Florian Bach ◽

Diana Munoz Sandoval ◽

Michalina Mazurczyk ◽

Yrene Themistocleous ◽

Thomas A Rawlinson ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Plasmodium Vivax ◽

T Cell Activation ◽

Cell Activation ◽

Parasite Species ◽

Field Isolate ◽

Effector Memory ◽

Lymphoid Tissues ◽

Systems Immunology

Plasmodium vivax offers unique challenges for malaria control and may prove a more difficult species to eradicate than Plasmodium falciparum. Yet compared to P. falciparum we know very little about the innate and adaptive immune responses that need to be harnessed to reduce disease and transmission. In this study, we inoculated human volunteers with a clonal field isolate of P. vivax and used systems immunology tools to track their response through infection and convalescence. Our data reveal Plasmodium vivax triggers an acute phase response that shares remarkable overlap with that of P. falciparum, suggesting a hardwired innate response that does not differentiate between parasite species. This leads to the global recruitment of innate-like and adaptive T cells into lymphoid tissues where up to one quarter of the T cell compartment is activated. Heterogeneous effector memory-like CD4+ T cells dominate this response and their activation coincides with collateral tissue damage. Remarkably, comparative transcriptional analyses show that P. falciparum drives even higher levels of T cell activation; diverging T cell responses may therefore explain why falciparum malaria more frequently causes severe disease.

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Clinical and multi-omics cross-phenotyping of patients with autoimmune and autoinflammatory diseases: the observational TRANSIMMUNOM protocol

BMJ Open ◽

10.1136/bmjopen-2017-021037 ◽

2018 ◽

Vol 8 (8) ◽

pp. e021037 ◽

Cited By ~ 2

Author(s):

Roberta Lorenzon ◽

Encarnita Mariotti-Ferrandiz ◽

Caroline Aheng ◽

Claire Ribet ◽

Ferial Toumi ◽

...

Keyword(s):

Systems Biology ◽

Good Clinical Practice ◽

Autoinflammatory Diseases ◽

Case Report Form ◽

Sample Collection ◽

Clinical Protocol ◽

Link Type ◽

Systems Immunology ◽

Hospital Ethics ◽

Set Up

IntroductionAutoimmune and autoinflammatory diseases (AIDs) represent a socioeconomic burden as the second cause of chronic illness in Western countries. In this context, the TRANSIMMUNOM clinical protocol is designed to revisit the nosology of AIDs by combining basic, clinical and information sciences. Based on classical and systems biology analyses, it aims to uncover important phenotypes that cut across diagnostic groups so as to discover biomarkers and identify novel therapeutic targets.Methods and analysisTRANSIMMUNOM is an observational clinical protocol that aims to cross-phenotype a set of 19 AIDs, six related control diseases and healthy volunteers . We assembled a multidisciplinary cohort management team tasked with (1) selecting informative biological (routine and omics type) and clinical parameters to be captured, (2) standardising the sample collection and shipment circuit, (3) selecting omics technologies and benchmarking omics data providers, (4) designing and implementing a multidisease electronic case report form and an omics database and (5) implementing supervised and unsupervised data analyses.Ethics and disseminationThe study was approved by the institutional review board of Pitié-Salpêtrière Hospital (ethics committee Ile-De-France 48–15) and done in accordance with the Declaration of Helsinki and good clinical practice. Written informed consent is obtained from all participants before enrolment in the study. TRANSIMMUNOM’s project website provides information about the protocol (https://www.transimmunom.fr/en/) including experimental set-up and tool developments. Results will be disseminated during annual scientific committees appraising the project progresses and at national and international scientific conferences.DiscussionSystems biology approaches are increasingly implemented in human pathophysiology research. The TRANSIMMUNOM study applies such approach to the pathophysiology of AIDs. We believe that this translational systems immunology approach has the potential to provide breakthrough discoveries for better understanding and treatment of AIDs.Trial registration numberNCT02466217; Pre-results.

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The chromatin accessibility signature of human immune aging stems from CD8+ T cells

Journal of Experimental Medicine ◽

10.1084/jem.20170416 ◽

2017 ◽

Vol 214 (10) ◽

pp. 3123-3144 ◽

Cited By ~ 63

Author(s):

Duygu Ucar ◽

Eladio J. Márquez ◽

Cheng-Han Chung ◽

Radu Marches ◽

Robert J. Rossi ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Cd8 T Cells ◽

Chromatin Accessibility ◽

T Cell Signaling ◽

Memory Cd8 T Cells ◽

Systems Immunology ◽

Human Immune ◽

Chromatin Opening ◽

Il7r Gene

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency.

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