Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The long-lasting clinical response by lymphoma patients to anti-CD20 therapy has been attributed to the induction of an anti-tumor adaptive immunity. We previously demonstrated that a CD4-dependent mechanism is responsible for the long-term protection of CD20(+) tumor-bearing mice by anti-CD20 treatment. Here, we compare tumor immunity in tumor-bearing animals that did or did not receive anti-CD20 treatment. Splenic CD4(+)FoxP3(+) regulatory T cells (Tregs) expanded substantially in untreated mice that exhibited then a reduced survival, whereas Tregs depletion led to long-term survival of the animals, suggesting the establishment of a Treg-dependent immunosuppressive environment after tumor injection. Strikingly, anti-CD20 therapy reversed the initial expansion of Tregs, and was accompanied by a marked increase in the number of Th1 cells, with no detectable change in Th2 and Th17 cell numbers. Interleukin-12 serum level was also increased by the anti-CD20 treatment, and activated myeloid dendritic cells producing interleukin-12 could be detected in lymph nodes of treated animals, while interferon-γ blockade strongly reduced survival. Also, CD4(+) effector memory T cells were evidenced in surviving animals, and the transfer of CD4(+) T cells induced long-term protection. Thus, anti-CD20 therapy promotes strong anti-tumor adaptive immunity, opposes Treg expansion and inhibits tumor cells from maintaining an immunosuppressive environment.

Original publication

DOI

10.1038/leu.2014.275

Type

Journal article

Journal

Leukemia

Publication Date

04/2015

Volume

29

Pages

947 - 957

Keywords

Adaptive Immunity, Animals, Antibodies, Monoclonal, Murine-Derived, Antigens, CD4, Antineoplastic Agents, Cell Proliferation, Female, Forkhead Transcription Factors, Gene Expression Regulation, Leukemic, Immunologic Memory, Interferon-gamma, Interleukin-12, Lymph Nodes, Lymphoma, B-Cell, Mice, Mice, Inbred C57BL, Rituximab, Signal Transduction, Survival Analysis, T-Lymphocytes, Regulatory, Th1 Cells, Th17 Cells, Th2 Cells