A topic modeling approach reveals the dynamic T cell composition of peripheral blood during cancer immunotherapy Journal Article
| Authors: | Peng, X.; Lee, J.; Adamow, M.; Maher, C.; Postow, M. A.; Callahan, M. K.; Panageas, K. S.; Shen, R. |
| Article Title: | A topic modeling approach reveals the dynamic T cell composition of peripheral blood during cancer immunotherapy |
| Abstract: | We present TopicFlow, a computational framework for flow cytometry data analysis of patient blood samples for the identification of functional and dynamic topics in circulating T cell population. This framework applies a Latent Dirichlet Allocation (LDA) model, adapting the concept of topic modeling in text mining to flow cytometry. To demonstrate the utility of our method, we conducted an analysis of ∼17 million T cells collected from 138 peripheral blood samples in 51 patients with melanoma undergoing treatment with immune checkpoint inhibitors (ICIs). Our study highlights three latent dynamic topics identified by LDA: a T cell exhaustion topic that independently recapitulates the previously identified LAG-3+ immunotype associated with ICI resistance, a naive topic and its association with immune-related toxicity, and a T cell activation topic that emerges upon ICI treatment. Our approach can be broadly applied to mine high-parameter flow cytometry data for insights into mechanisms of treatment response and toxicity. © 2023 The Author(s) |
| Keywords: | adult; treatment response; aged; major clinical study; flow cytometry; neoplasm; neoplasms; t lymphocyte; t-lymphocytes; quality control; cancer immunotherapy; melanoma; pharmacodynamics; cluster analysis; drug resistance; immunotherapy; blood sampling; data analysis; computer model; dynamics; t lymphocyte activation; phase 2 clinical trial (topic); data mining; immune checkpoint inhibitor; very elderly; humans; human; male; female; article; cp: immunology; cp: cancer biology |
| Journal Title: | Cell Reports Methods |
| Volume: | 3 |
| Issue: | 8 |
| ISSN: | 2667-2375 |
| Publisher: | Cell Press |
| Date Published: | 2023-08-28 |
| Start Page: | 100546 |
| Language: | English |
| DOI: | 10.1016/j.crmeth.2023.100546 |
| PUBMED: | 37671017 |
| PROVIDER: | scopus |
| PMCID: | PMC10475788 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding authors are MSK authors: Margaret K. Callahan, Katherine S. Panageas, Ronglai Shen -- Source: Scopus |
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