Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity

Michael D. Nissen, Manabu Kusakabe, Xuehai Wang, Guillermo Simkin, Deanne Gracias, Kateryna Tyshchenko, Ainsleigh Hill, Justin Meskas, Stacy Hung, Elizabeth A. Chavez, Daisuke Ennishi, Tomohiro Aoki, Clementine Sarkozy, Joseph M. Connors, Pedro Farinha, Graham W. Slack, Randy D. Gascoyne, Ryan R. Brinkman, David W. Scott, Christian SteidlAndrew P. Weng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell-of-origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B-cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B-cells from each patient occupied unique regions in 37-dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case, we were able to demonstrate direct correspondence between protein-level phenotypic subsets and DNA mutation-defined subclones. In summary, CyTOF analysis can resolve both intertumoral and intratumoral heterogeneity among primary samples and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones.

Original languageEnglish
Pages (from-to)620-629
Number of pages10
JournalCytometry Part A
Volume97
Issue number6
DOIs
Publication statusPublished - Jun 1 2020
Externally publishedYes

Keywords

  • CyTOF
  • DLBCL
  • EZH2
  • FACS
  • HLA-DR
  • Mass cytometry
  • cell-of-origin
  • flow cytometry
  • lymph node
  • lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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  • Cite this

    Nissen, M. D., Kusakabe, M., Wang, X., Simkin, G., Gracias, D., Tyshchenko, K., Hill, A., Meskas, J., Hung, S., Chavez, E. A., Ennishi, D., Aoki, T., Sarkozy, C., Connors, J. M., Farinha, P., Slack, G. W., Gascoyne, R. D., Brinkman, R. R., Scott, D. W., ... Weng, A. P. (2020). Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity. Cytometry Part A, 97(6), 620-629. https://doi.org/10.1002/cyto.a.23919