Abstract 3636: Anti-CD20 therapy prevents protumor regulatory T-cell expansion and triggers a memory Th1 response in tumor-bearing mice

Abstract

Abstract The long-lasting clinical response by lymphoma patients to anti-CD20 treatment has been attributed to a ‘vaccinal’-type effect through the induction of an anti-tumor adaptive immunity. Using a model where C57Bl/6 mice were injected intravenously with EL4 tumor cells expressing human CD20, we previously showed that CD4 cells are central to the host protection induced by anti-CD20 therapy. Here, we have first shown that the transfer of highly purified CD4+ T cells induces a long-term protection, demonstrating that this T-cell subset plays indeed a key role in the induction of an adaptive memory response. In addition, CD4+ effector memory T cells were detected in surviving animals. We have then analyzed the changes occurring in various T cell subsets in tumor-bearing animals receiving anti-CD20 treatment. On the one hand, untreated animals exhibited a large expansion of CD4+FoxP3+ regulatory T cells (Tregs), with reduced survival. Depletion of these cells using anti-CD25 injection led to long-term survival, indicating that a Treg-dependent immuno-suppressive environment is established after tumor injection in this model. On the other hand, anti-CD20 therapy, that induces a long-lasting protection, reversed the initial expansion of Tregs one week after the end of anti-CD20 treatment, and was accompanied by a marked increase in the number of Th1 cells. Concomitantly, an increase in the serum levels of interleukin-12 was observed, as well as an increased in the number of activated myeloid dendritic cells producing this cytokine. Moreover, a strong decrease in the survival was observed when Natural Killer cells were depleted using anti-asialo GM1 antibodies or following neutralization of interferon-γ. Thus, the host protection elicited by anti-CD20 treatment involves a network of cells from both innate and adaptive immunity that both are needed for long-term protection. In conclusion, our work demonstrates that anti-CD20 therapy promotes a strong anti-tumor adaptive immunity, opposes Treg expansion, and that a pro-tumor immune contexture shaped by the presence of growing tumor cells can be reversed by antibody treatment. Citation Format: Claire Deligne, Sophie Siberil, Jean-Luc Teillaud. Anti-CD20 therapy prevents protumor regulatory T-cell expansion and triggers a memory Th1 response in tumor-bearing mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3636. doi:10.1158/1538-7445.AM2014-3636