The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4(+) and CD8(+), FOXP3(+)CD25(bright) Treg, and "innate-like" CD56(+)) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4(+) T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4(+) T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4(+) and CD8(+) T cell subsets associated with higher frequencies of IFNγ(+) and GrzB(+) cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy / Battella, Simone; Cox, M. Christina; LA SCALEIA, Raffaella; DI NAPOLI, Arianna; Di Landro, Francesca; Porzia, Alessandra; Franchitti, Lavinia; Mainiero, Fabrizio; Ruco, Luigi; Monarca, Bruno; Santoni, Angela; Palmieri, Gabriella. - In: CANCER IMMUNOLOGY, IMMUNOTHERAPY. - ISSN 0340-7004. - 66:10(2017), pp. 1295-1306. [10.1007/s00262-017-2026-7]

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy

BATTELLA, SIMONE;LA SCALEIA, RAFFAELLA;DI NAPOLI, Arianna;PORZIA, Alessandra;FRANCHITTI, LAVINIA;MAINIERO, Fabrizio;RUCO, Luigi;MONARCA, Bruno;SANTONI, Angela;PALMIERI, Gabriella
2017

Abstract

The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4(+) and CD8(+), FOXP3(+)CD25(bright) Treg, and "innate-like" CD56(+)) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. At diagnosis, DLBCL patients showed lower lymphocyte counts, due to selective decrement of CD4(+) T (including Treg) and B lymphocytes. While all T cell subsets transiently decreased during therapy, CD4(+) T cell and Treg remained significantly lower than controls, up to 1 year after R-CHOP. Phenotypically skewed profile of CD4(+) and CD8(+) T cell subsets associated with higher frequencies of IFNγ(+) and GrzB(+) cells at diagnosis, that transiently decreased during therapy, and re-attained persistently elevated levels, till up to 1 year after therapy. Differently, the pre-therapy elevated levels of circulating monocytes, and of plasma IL-6 and IL-10 rapidly normalized upon R-CHOP. In sum, we describe a quantitatively and functionally altered status of the peripheral blood T cell compartment in DLBCL patients at diagnosis, that persists long-term after tumor eradication, and it is only transiently perturbed by R-CHOP chemoimmunotherapy. Moreover, data suggest the association of selected T cell functional features with DLBCL phenotype, and with therapy outcome.
2017
CD4+ and CD8+ T lymphocytes; Chemoimmunotherapy; DLBCL, diffuse large B cell lymphoma; IFNγ; Long-term immune profiling; Rituximab
01 Pubblicazione su rivista::01a Articolo in rivista
Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy / Battella, Simone; Cox, M. Christina; LA SCALEIA, Raffaella; DI NAPOLI, Arianna; Di Landro, Francesca; Porzia, Alessandra; Franchitti, Lavinia; Mainiero, Fabrizio; Ruco, Luigi; Monarca, Bruno; Santoni, Angela; Palmieri, Gabriella. - In: CANCER IMMUNOLOGY, IMMUNOTHERAPY. - ISSN 0340-7004. - 66:10(2017), pp. 1295-1306. [10.1007/s00262-017-2026-7]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/972905
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