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

Abstract

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.

Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma

“…Taken together, our results suggest that various PET parameters may capture distinct underlying tumor biology with different prognostic implications, as recently demonstrated in follicular lymphoma. 43 …”

Expression of glucose transporter-1 in follicular lymphoma affected tumor-infiltrating immunocytes and was related to progression of disease within 24 months

“…Recent study disclosed that due to the number advantages of B cells in FL, the relative contribution of intratumoral T cells to TMTV was limited, as proved that CD4+ Tfh and activated CD8+ T cells were clonally expanded in low TMTV status compared to those with a high TMTV. Pretherapy TMTV based on 18F-fluorodeoxyglucose uptake best reflects the malignant B-cell burden and maximum standardized uptake value (SUVmax) was influenced by intratumoral T cells [33] . However, these two parameters always present the inconsistent trend and could not reflect the complete metabolic process of tumor.…”

A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma

“…Total metabolic tumor volume and SUVmax have been postulated as parameters reflecting different cell compartments. While TMTV best reflects the malignant B‐cell burden, intratumoral T cells influence SUVmax, and this can be dependent on the treatment regimen 29 . Due to the small number of patients with an SUVmax <5, the absence of independent impact of TLG on TTFT, the more consolidated role of TMTV in other settings in FL 19 and the contradicting results regarding TLG and SUVmax in previous studies, 30 we focused our analysis on the impact of TMTV.…”