Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma

Data on the prognostic impact of pretherapy 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in follicular lymphoma (FL) is conflicting. The predictive utility of pretherapy total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) on outcome appears to vary between regimens. Chemoimmunotherapies vary in the extent of T-cell depletion they induce. The role of intratumoral T cells on pretherapy FDG-PET parameters is undefined. We assessed pretherapy FDG-PET parameters and quantified intratumoral T cells by multiple methodologies. Low intratumoral T cells associated with approximately sixfold higher TMTV, and FL nodes from patients with high TMTV showed increased malignant B-cell infiltration and fewer clonally expanded intratumoral CD8+ and CD4+ T-follicular helper cells than those with low TMTV. However, fluorescently labeled glucose uptake was higher in CD4+ and CD8+ T cells than intratumoral B cells. In patients with FDG-PET performed prior to excisional biopsy, SUVmax within the subsequently excised node associated with T cells but not B cells. In summary, TMTV best reflects the malignant B-cell burden in FL, whereas intratumoral T cells influence SUVmax. This may contribute to the contradictory results between the prognostic role of different FDG-PET parameters, particularly between short- and long-term T-cell-depleting chemoimmunotherapeutic regimens. The impact of glucose uptake in intratumoral T cells should be considered when interpreting pretherapy FDG-PET in FL.