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.