Selective phenotypical and functional alterations of peripheral blood immune cells in neo-diagnosed patients with Diffuse Large B cell Lymphoma (DLBCL)

PURPOSE: To investigate the impact of lymphoid tumor presence on the asset of the systemic immune compartment. METHODS: Multiparameter FACS analysis and in vitro cytotoxicity assay were used to evaluate: 1) natural and CD16-mediated NK cytotoxic functions; 2) relative and absolute frequency, and 3) cytotoxic and IFN γ production capabilities of the main leukocyte subsets, in a cohort of 32 DLBCL patients at diagnosis and 27 healthy, age- and sex-matched controls. RESULTS: Patients showed a higher absolute monocyte number, and a lower lymphocyte count, mostly due to the selective diminution of CD4+ T cells (but not of Treg), and B lymphocytes. Accordingly, lymphocyte/monocyte and CD4/CD8 ratios decreased, while NK percentage increased. The phenotypically skewed profile of PBL associated with functional alterations, as: 1) IFN γ+ cells were increased among CD4+ and CD8+ T cell subsets, but not in CD56+ T and CD3-CD56+ NK cell populations; 2) a higher frequency of Granzyme B+ cells chara

PURPOSE: To investigate the impact of lymphoid tumor presence on the asset of the systemic immune compartment. METHODS: Multiparameter FACS analysis and in vitro cytotoxicity assay were used to evaluate: 1) natural and CD16-mediated NK cytotoxic functions; 2) relative and absolute frequency, and 3) cytotoxic and IFN γ production capabilities of the main leukocyte subsets, in a cohort of 32 DLBCL patients at diagnosis and 27 healthy, age- and sex-matched controls. RESULTS: Patients showed a higher absolute monocyte number, and a lower lymphocyte count, mostly due to the selective diminution of CD4+ T cells (but not of Treg), and B lymphocytes. Accordingly, lymphocyte/monocyte and CD4/CD8 ratios decreased, while NK percentage increased. The phenotypically skewed profile of PBL associated with functional alterations, as: 1) IFN γ+ cells were increased among CD4+ and CD8+ T cell subsets, but not in CD56+ T and CD3-CD56+ NK cell populations; 2) a higher frequency of Granzyme B+ cells characterized (CD4+ and CD8+) T and (CD56bright and CD56dim) NK cell subsets; noteworthy, natural and CD16-dependent NK cytotoxic activities were unchanged. IL-6 and IL-10 plasma levels were significantly higher in DLBCL. Selected alterations of patients' immunological profile differently correlated with the DLBCL Germinal Center B (GCB) vs non GCB-type and with the presence of bulky disease or the involvement of extra-nodal sites. DISCUSSION: Our findings show a deeply altered phenotypic and functional PBMC profile in newly-diagnosed DLBCL patients, with the lymphocyte compartment showing traits of chronic activation; moreover, distinct immunological alterations correlated with tumor histological subtype and clinical features. CONCLUSION: These results suggest that tumor presence deeply affects the immune status of the host, at the systemic level, in the context of the immune system/tumor cross-talk; they could be of relevance in the perspective of chemoimmunotherapeutical strategies.