Prognostic relevance of tumor-infiltrating CD4+ cells and total metabolic tumor volume-based risk stratification in diffuse large B-cell lymphoma

Abstract

To elucidate the relationship between pre-treatment radiomic parameters and the proportions of various tumour-infiltrating (TI) cells, we retrospectively analysed the association of total metabolic tumour volume (TMTV) and TI cells on biopsied tumour lesions in 171 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The surface markers of TI cells were analysed by multicolour flow cytometry using a dissected single-cell suspension. In examining the correlation between TI cells and PET-derived parameters (SUVmax, TMTV, and total lesion glycolysis), intratumoural cell types minimally influenced the results, except for a weak negative correlation between CD4+ cells and SUVmax (R=-0.16, P=0.045). Even for the lesion fluorodeoxyglucose uptake at the biopsied site, CD19+ cells (indicative of malignant burden) showed only a weak correlation with the highest SUV (R=0.21, P=0.009), whereas CD3+ (R=-0.25, P=0.002) and CD4+ cells (R=-0.29, P<0.001) demonstrated a similarly weak inverse correlation. High TMTV and low TI CD4+ cells were independently associated with poor prognosis and their combination identified the most adverse population (3-year progression-free survival: 32.3%, 95% confidence interval [CI]: 19.4%-53.7%; 3-year overall survival: 48.4%, 95% CI: 33.6%-69.6%). Moreover, radiomic parameters incorporating the international prognostic index significantly improved the 3-year survival prediction (area under the curve: 0.76, P<0.05) compared to their standalone use. This study underscores the prognostic impact of TI CD4+ cells on DLBCL and suggests that integration of TMTV and TI cell analysis enhances the accuracy of prognostic prediction.