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Ratios of CD8 T lymphocytes to M-MDSCs (CD8MMR) predict prognosis in patients with untreated DLBCL
Hao-Yuan Wang1,2, Fu-Chen Yang3, Ching-Fen Yang4
1Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus-positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.
CD8 and CD4 T lymphocytes play critical roles in antitumor immunity and are central to immune-based therapies for diffuse large B-cell lymphoma (DLBCL). Conversely, monocytic myeloid-derived suppressor cells (M-MDSCs) promote immunosuppression and tumor progression. This study investigates the prognostic value of the ratios of CD8 and CD4 T lymphocytes to M-MDSCs, referred to as CD8MMR and CD4MMR, in patients with untreated DLBCL. In a prospective observational study, 160 patients newly diagnosed with DLBCL were enrolled and randomized into training (n = 120) and validation (n = 40) cohorts. Circulating immune cells were assessed from fresh peripheral blood using flow cytometry, and cutoff values for CD8MMR and CD4MMR were determined by receiver operating characteristic curve and area under the curve analysis. Patients with high-risk International Prognostic Index (IPI), double-expressor lymphoma, or Epstein-Barr virus-positive DLBCL had significantly lower CD8MMR and CD4MMR. Low CD8MMR (<3.56) or CD4MMR (<3.79) was significantly associated with inferior progression-free survival (PFS) and overall survival (OS). When combining both ratios, patients with high levels of CD8MMR and CD4MMR had the most favorable survival, whereas those with low levels of both had the poorest outcomes; discordant levels corresponded to intermediate survival. Multivariate analysis revealed CD8MMR as an independent predictor of PFS and OS, with greater predictive strength than CD4MMR. Furthermore, CD8MMR stratified survival outcomes across different IPI risk categories and cell-of-origin subtypes, consistently identifying patients with poor prognosis. These findings suggest that CD8MMR is a novel and independent prognostic biomarker in DLBCL, offering additional value for risk stratification in clinical practice.
