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 (J.C.) Villasboas Bisneto, Tammy Price-Troska, Shahrzad Jalali, Hongyan Wu, Rebecca Luchtel, Mei-Yin Polley, Anne J Novak, Stephen Maxted Ansell

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Fingerprint

Follicular Lymphoma
T-cells
T-Lymphocyte Subsets
T-Lymphocytes
Survival
Tumor Microenvironment
Biopsy
Population
Cluster Analysis
Lymphoma
B-Lymphocytes
Tumors
Cell Count
Cells
Tissue
Data storage equipment

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mass Cytometry Analysis Reveals that Specific Intratumoral CD4 + T Cell Subsets Correlate with Patient Survival in Follicular Lymphoma . / Yang, Zhi Zhang; Kim, Hyo Jin; Villasboas Bisneto, Jose (J.C.); Price-Troska, Tammy; Jalali, Shahrzad; Wu, Hongyan; Luchtel, Rebecca; Polley, Mei-Yin; Novak, Anne J; Ansell, Stephen Maxted.

In: Cell reports, Vol. 26, No. 8, 19.02.2019, p. 2178-2193.e3.

Research output: Contribution to journalArticle

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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.",
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