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


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.

SUBMITTER: Yang ZZ 

PROVIDER: S-EPMC6402596 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Mass Cytometry Analysis Reveals that Specific Intratumoral CD4<sup>+</sup> T Cell Subsets Correlate with Patient Survival in Follicular Lymphoma.

Yang Zhi-Zhang ZZ   Kim Hyo Jin HJ   Villasboas Jose C JC   Price-Troska Tammy T   Jalali Shahrzad S   Wu Hongyan H   Luchtel Rebecca A RA   Polley Mei-Yin C MC   Novak Anne J AJ   Ansell Stephen M SM  

Cell reports 20190201 8


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<sup>+</sup> 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<sup>+</sup> T cell numbers were not associated with patient outcome, s  ...[more]

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