CD4+Foxp3-IL-10+ Tr1 Cells Promote Relapse of Diffuse Large B Cell Lymphoma by Enhancing the Survival of Malignant B Cells and Suppressing Antitumor T Cell Immunity.
Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy. Complete remission can be achieved in most patients by conventional treatment with rituximab and chemotherapy. However, a subset of remission individuals will develop a relapsed disease for obscure reasons. CD4+Foxp3-IL-10+ cell (Tr1) is a novel cell subtype with the capacity to suppress pro-inflammatory responses, but has not been extensively studied in most tumors. In this study, we investigated the potential role of Tr1 cells in DLBCL. We found that compared to that in healthy controls, the frequency of Tr1 cells was significantly increased in DLBCL patients, even during complete remission. Further study showed that these Tr1 cells were enriched in the CD25low/-Foxp3-CD49b+LAG-3+ fraction and could be developed in vitro from naive CD45RA+ CD4+ T cells. To examine the effect of Tr1 upregulation, we cocultured the enriched in vitro-induced Tr1 cells (iTr1) with autologous primary DLBCL cells and CD3+ T cells and found that iTr1 cells both enhanced the survival of CD20+ DLBCL tumor cells and suppressed the antitumor response of CD3+ T cells through the production of IL-10. Furthermore, the frequency of CD4+Foxp3-IL-10+ Tr1 cells in DLBCL patients during complete remission is directly associated with the risk of relapse. Together, these results suggested that Tr1 cells contributed to tumor cell maintenance and may serve as a prognostic marker and therapeutic target.
['Liu|Guozhen|G|', 'Luan|Jing|J|', 'Li|Qiang|Q|']
D000328:Adult D000368:Aged D058846:Antibodies, Monoclonal, Murine-Derived D015703:Antigens, CD D000971:Antineoplastic Combined Chemotherapy Protocols D001402:B-Lymphocytes D015704:CD4 Antigens D015496:CD4-Positive T-Lymphocytes D016022:Case-Control Studies D002470:Cell Survival D018920:Coculture Techniques D003520:Cyclophosphamide D004317:Doxorubicin D005260:Female D051858:Forkhead Transcription Factors D015870:Gene Expression D006801:Humans D016130:Immunophenotyping D039421:Integrin alpha2 D016753:Interleukin-10 D018655:Lymphocyte Count D016403:Lymphoma, Large B-Cell, Diffuse D008297:Male D008875:Middle Aged D011241:Prednisone D061251:Primary Cell Culture D011379:Prognosis D012008:Recurrence D012074:Remission Induction D000069283:Rituximab D014750:Vincristine
Tr1 cell DLBCL