A map of tumor–host interactions in glioma at single-cell resolution

  1. Francesca Pia Caruso
  2. Luciano Garofano
  3. Fulvio D'Angelo
  4. Kai Yu
  5. Fuchou Tang
  6. Jinzhou Yuan
  7. Jing Zhang
  8. Luigi Cerulo
  9. Stefano M Pagnotta
  10. Davide Bedognetti
  11. Peter A Sims
  12. Mario Suvà
  13. Xiao-Dong Su
  14. Anna Lasorella
  15. Antonio Iavarone
  16. Michele Ceccarelli

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Abstract

Background

Single-cell RNA sequencing is the reference technique for characterizing the heterogeneity of the tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is of fundamental importance for the identification of immuno-oncology therapeutic targets.

Results

We present a novel method, single-cell Tumor–Host Interaction tool (scTHI), to identify significantly activated ligand–receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand–receptor interactions in glioma using 6 publicly available human glioma datasets encompassing 57,060 gene expression profiles from 71 patients. By leveraging this large-scale collection we show that unexpected cross-talk partners are highly conserved across different datasets in the majority of the tumor samples. This suggests that shared cross-talk mechanisms exist in glioma.

Conclusions

Our results provide a complete map of the active tumor–host interaction pairs in glioma that can be therapeutically exploited to reduce the immunosuppressive action of the microenvironment in brain tumor.

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  1. GigaScience

    Now published in GigaScience doi: 10.1093/gigascience/giaa109

    Francesca Pia Caruso 1Department of Science and Technologies, Università degli Studi del Sannio, 82100, Benevento, Italy2Bioinformatics Lab, BIOGEM, Ariano Irpino, ItalyFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteLuciano Garofano 1Department of Science and Technologies, Università degli Studi del Sannio, 82100, Benevento, Italy3Institute for Cancer Genetics, Columbia University, New York (NY), USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFulvio D’Angelo 2Bioinformatics Lab, BIOGEM, Ariano Irpino, Italy3Institute for Cancer Genetics, Columbia University, New York (NY), USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteKai Yu 4Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFuchou Tang 4Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteJinzhou Yuan 5Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA6Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteJing Zhang 3Institute for Cancer Genetics, Columbia University, New York (NY), USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteLuigi Cerulo 1Department of Science and Technologies, Università degli Studi del Sannio, 82100, Benevento, Italy2Bioinformatics Lab, BIOGEM, Ariano Irpino, ItalyFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteDavide Bedognetti 7Cancer Program, Sidra Medicine, Doha, QatarFind this author on Google ScholarFind this author on PubMedSearch for this author on this sitePeter A. Sims 5Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA6Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteMario Suvà 8Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA9Broad Institute of Harvard and MIT, Cambridge, MA 02142, USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteXiao-Dong Su 4Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, ChinaFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteAnna Lasorella 3Institute for Cancer Genetics, Columbia University, New York (NY), USA10Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteAntonio Iavarone 3Institute for Cancer Genetics, Columbia University, New York (NY), USA10Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA11Department of Neurology, Columbia University Medical Center, New York, NY, USAFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteMichele Ceccarelli 2Bioinformatics Lab, BIOGEM, Ariano Irpino, Italy12Department of Electrical Engineering and Information Technology (DIETI), University of Naples “Federico II”, ItalyFind this author on Google ScholarFind this author on PubMedSearch for this author on this siteFor correspondence: michele.ceccarelli@unina.it

    A version of this preprint has been published in the Open Access journal GigaScience (see paper https://doi.org/10.1093/gigascience/giaa109 ), where the paper and peer reviews are published openly under a CC-BY 4.0 license.

    These peer reviews were as follows:

    Reviewer 1: http://dx.doi.org/10.5524/REVIEW.102411 Reviewer 2: http://dx.doi.org/10.5524/REVIEW.102412 Reviewer 3: http://dx.doi.org/10.5524/REVIEW.102413

  2. Version published to 10.1093/gigascience/giaa109
  3. Version published to 10.1101/827758v1 on bioRxiv