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Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing

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Abstract

An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated. We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME. We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors. We also applied CellChat to analyze the complex interactions among the infiltrated immune cells. Our data revealed significant infiltration of B cells in addition to other important immune cells, including CD4+, CD8+, and NK cells following virotherapy. Further analysis identified distinct subset compositions of the infiltrated immune cells and their activation status upon virotherapy. The intensive interactions among the infiltrated immune cells as revealed by CellChat analysis may further shape the immune landscape in favor of generating antitumor immunity. Our findings will facilitate the design of new strategies in incorporating immunotherapy into virotherapy for clinical translation. Moreover, the significant infiltration of B cells makes it suitable for combining virotherapy with immune checkpoint inhibitors.

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Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The raw scRNA-seq data is available on the GEO database (GEO accession number GSE186548). The materials will be available upon request with a simple MTA.

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Acknowledgements

This work was supported by the Cancer Prevention and Research Institute of Texas (CPRIT) grant RP200464 and a grant from the William and Ella Owens Medical Research Foundation (to X.Z.), the National Institutes of Health grant R01LM012806 (to Z.Z), and the CPRIT grant RP180734 (to Z.Z.). We thank the University of Houston sequencing core for library construction and sequencing, and Dr. Brandon Mistretta for his assistance with pre-processing and upstream analysis of the scRNA-seq data. We thank Dr. Xinli Liu for assistance with the cell sorting, and Dr. Wanfu Wu for assistance with IHC staining. We also thank Drs. Weiyi Peng and Navin Varadarajan for advice, and Dr. Tho Tran for careful reading of the manuscript.

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Authors and Affiliations

  1. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA

    Divya Ravirala & Xiaoliu Zhang

  2. Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

    Guangsheng Pei & Zhongming Zhao

  3. Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

    Zhongming Zhao

  4. University of Houston, SERC 3004, 3517 Cullen Blvd, Houston, TX, 77204, USA

    Xiaoliu Zhang

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  1. Divya Ravirala
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  2. Guangsheng Pei
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Contributions

D.R and X.Z. conceived the project and designed the experiments. D.R. executed all the experiments in the study. G.P. and D.R. performed bioinformatics analysis. D.R. and X.Z. wrote the manuscript draft and G.P. and Z.Z. helped the finalization of the manuscript.

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Correspondence to Xiaoliu Zhang.

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Ravirala, D., Pei, G., Zhao, Z. et al. Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing. Cancer Immunol Immunother 71, 1479–1495 (2022). https://doi.org/10.1007/s00262-021-03084-2

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