Recovery of central memory and naive peripheral t cells in follicular Lymphoma patients receiving rituximab-chemotherapy based regimen
Résumé
Preclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on t-cell immunity. We have performed a prospective study of peripheral t-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4 + t eM , CD4 + t reg and CD8 + t eMRA subsets and significant amounts of CD38 + HLA-DR + activated T cells. A portion of these activated/differentiated T cells also expressed PD-1 and/or TIGIT immune checkpoints. Hierarchical clustering of phenotyping data revealed that 5/8 patients with only a partial response to R-cHop induction therapy or with disease progression segregate into a group exhibiting a highly activated/differentiated T cell profile and a markedly low proportion of naive T cells before treatment. Rituximab-based therapy induced a shift of CD4 + and CD8 + t cells toward a central memory phenotype and of CD8 + T cells to a naive phenotype. In parallel, a decrease in the number of peripheral T cells expressing both PD-1 and TIGIT was detected. These observations suggest that the standard rituximab-based therapy partially reverts the profound alterations observed in t-cell subsets in FL patients, and that blood T-cell phenotyping could provide a better understanding of the mechanisms of rituximab-based treatment. Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL). Its clinical course is highly variable and survival medians are 7-15 years depending on the studies. Follicular lymphoma management is characterized by a risk-adapted therapy based on the stage of the disease and the symptoms of the patients. For high tumor burden patients, treatment options could be either rituximab plus cyclophosphamide, vincristine and prednisone with (R-CHOP) or without (R-CVP) doxorubicin or other anthracyclines, or rituxi-mab plus fludarabine for patients not eligible for anthracyclines, or rituximab plus bendamustine. Experimental therapies as well as allogeneic stem cell transplantation are rather considered for relapsed and more refractory disease 1. The addition of the anti-CD20 monoclonal antibody (mAb) rituximab to chemotherapy has resulted in a higher rate of complete remission and improved survival 2. In addition, rituximab as maintenance therapy
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