Mass Cytometry Analysis Reveals that Specific Intratumoral CD4 + T Cell Subsets Correlate with Patient Survival in Follicular Lymphoma

Zhi Zhang Yang*, Hyo Jin Kim, Jose C. Villasboas, Tammy Price-Troska, Shahrzad Jalali, Hongyan Wu, Rebecca A. Luchtel, Mei Yin C. Polley, Anne J. Novak, Stephen M. Ansell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Follicular lymphoma (FL) is an indolent B cell malignancy characterized by an extensive but poorly functional T cell infiltrate in the tumor microenvironment. Using mass cytometry, we identified at least 12 subsets of intratumoral CD4 + T cells, 3 of which were unique to FL biopsies versus control tissues. Of these subsets, the frequency of naive T cells correlated with improved patient survival. Although total PD-1 + T cell numbers were not associated with patient outcome, specific PD-1 + T cell subpopulations were associated with poor survival. Intratumoral T cells lacking CD27 and CD28 co-stimulatory receptor expression were enriched in FL and correlated with inferior patient outcomes. In vitro models revealed that CD70 + lymphoma cells played an important role in expanding this population. Taken together, our mass cytometry results identified CD4 + memory T cell populations that are poorly functional due to loss of co-stimulatory receptor expression and are associated with an inferior survival in FL. Yang et al. utilize mass cytometry (CyTOF) to characterize intratumoral T cells and explore the clinical relevance of T cell subsets in follicular lymphoma (FL). Clustering analysis reveals an immune signature with reduced expression of co-stimulatory molecules on intratumoral T cells that correlated with a poor prognosis in FL.

Original languageEnglish (US)
Pages (from-to)2178-2193.e3
JournalCell reports
Volume26
Issue number8
DOIs
StatePublished - Feb 19 2019

Funding

We thank Mr. Sean Murray and Dr. Heather Brown for the technical assistance of use CyTOF II. This work was supported by grants from the NIH ( P50 CA97274 ), the Leukemia & Lymphoma Society ( 6544-18-01 ), the Landow Foundation ( 91314990 ), the Jaime Erin Follicular Lymphoma Research Consortium ( 91314125 ), and the Predolin Foundation ( 91314099 ). We thank Mr. Sean Murray and Dr. Heather Brown for the technical assistance of use CyTOF II. This work was supported by grants from the NIH (P50 CA97274), the Leukemia & Lymphoma Society (6544-18-01), the Landow Foundation (91314990), the Jaime Erin Follicular Lymphoma Research Consortium (91314125), and the Predolin Foundation (91314099).

Keywords

  • CD27
  • CD4 CD25 regulatory T cells
  • CyTOF
  • PD-1
  • co-stimulatory receptor
  • follicular lymphoma
  • immune signature
  • intratumoral CD4 T cell
  • mass cytometry
  • patient survival

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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