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

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.