Advancing systems immunology through data-driven statistical analysis

Fong, Linda; Muñoz-Rojas, Andrés R; Miller‐Jensen, Kathryn

doi:10.1016/j.copbio.2018.03.009

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…522 ► Advancing systems immunology through data-driven statistical analysis. 523 Benchmark assessment of algorithms is a helpful resource when deciding what algorithms to use, although it is recommended to use multiple algorithms to ensure the validity of analysis results. ► Critical assessment of automated flow cytometry data analysis techniques.…”

Section: Discussionmentioning

confidence: 99%

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Hu‐Lieskovan

Bhaumik

Dhodapkar

et al. 2020

J Immunother Cancer

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Since the publication of the Society for Immunotherapy of Cancer’s (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.

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Section: Discussionmentioning

confidence: 99%

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Hu‐Lieskovan

Bhaumik

Dhodapkar

et al. 2020

J Immunother Cancer

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“…Vaccine development in the twenty-first century is enabled by increasingly sophisticated genetic and high-dimensional assays, aided by bioinformatics approaches ( 212 – 214 ). This has allowed unprecedented resolution, at the whole-systems level, of how innate, adaptive, and cellular immune responses are generated, interact, and are maintained after vaccination.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Current Challenges in Vaccinology

et al. 2020

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The development of vaccines, which prime the immune system to respond to future infections, has led to global declines in morbidity and mortality from dreadful infectious communicable diseases. However, many pathogens of public health importance are highly complex and/or rapidly evolving, posing unique challenges to vaccine development. Several of these challenges include an incomplete understanding of how immunity develops, host and pathogen genetic variability, and an increased societal skepticism regarding vaccine safety. In particular, new high-dimensional omics technologies, aided by bioinformatics, are driving new vaccine development (vaccinomics). Informed by recent insights into pathogen biology, host genetic diversity, and immunology, the increasing use of genomic approaches is leading to new models and understanding of host immune system responses that may provide solutions in the rapid development of novel vaccine candidates.

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“…This concept supports the increased relevance of high-throughput assays and data collection at single-cell resolution. A recent review highlighted examples of data-driven systems modeling that characterize, map, or connect components of the immune system, with application in cancer immunotherapy (43). In the next sections, we will provide examples of the application of one or more high-throughput multi-parametric technologies for the identification of predictors of response to immunotherapy.…”

Section: Integration Of Large Datasets and Biological Interpretationmentioning

confidence: 99%

Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy

et al. 2020

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Immunotherapy, particularly immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, holds a great promise against cancer. These treatments have markedly improved survival in solid as well as in hematologic tumors previously considered incurable. However, durable responses occur in a fraction of patients, and existing biomarkers (e.g. PD-L1) have shown limited prediction power. This scenario highlights the need to dissect the complex interplay between immune and tumor cells to identify reliable biomarkers of response to be used for patients' selection. In this context, systems immunology represents indeed the new frontier to address important clinical challenges in biomarker discovery. Through the integration of multiple layers of data obtained with several high-throughput approaches, systems immunology may give insights on the vast range of inter-individual differences and on the influences of genes and factors that cooperatively shape the individual immune response to a given treatment. In this Mini Review, we give an overview of the current high-throughput methodologies, including genomics, epigenomics, transcriptomics, metabolomics, proteomics, and multiparametric phenotyping suitable for systems immunology as well as on the key steps of data integration and biological interpretation. Additionally, we review recent studies in which multi-omics technologies have been used to characterize mechanisms of response and to identify powerful biomarkers of response to checkpoint inhibitors, CART cell therapy, dendritic cell-based and peptide-based cancer vaccines. We also highlight the need of favoring the collaboration of researchers with complementary expertise and of integrating multi-omics data into biological networks with the final goal of developing accurate markers of therapeutic response.

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Advancing systems immunology through data-driven statistical analysis

Cited by 8 publications

References 56 publications

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Current Challenges in Vaccinology

Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy

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