To the Editor:

In the August issue of Cancer Research, Inoue et al. reported a mechanism by which B cells inhibit the immune response against tumors. Their results support a model whereby B cell stimulation via CD40 leads to diminished CD8 and natural killer cell–mediated IFN-γ secretion and thereby attenuates antitumor immunity (1).

Their results are in line with findings previously published in 2005 in our own article entitled “Increased Rejection of Primary Tumors in Mice Lacking B Cells: Inhibition of Antitumor CTL and TH1 Cytokine Responses by B Cells” (2).

In that study, we reported that B cell–deficient mice (BCDM) have greater immunologic resistance to tumor, and that the increased resistance is associated with an enhanced antitumor Th1 cytokine and CTL response.

We used the MC38 tumor model to show that B cells inhibited secretion of IFN-γ from T cells in vitro in a CD40-dependent manner. However, there was no difference in tumor growth in an adoptive transfer experiment in which BCDM were reconstituted with either wild-type or CD40−/− B cells, indicating that CD40 may play a lesser role in inhibiting antitumor T cell response in vivo.

Using the EL-4 tumor model, Inoue et al. showed that IL-10 production from B cells might be responsible for decreased IFN-γ response seen in vitro.

Because we saw discordant results when comparing IFN-γ response in vitro to the effects of B cell reconstitution in vivo, it remains to be seen whether IL-10–producing B cells are responsible for the inhibition of antitumor Th1 and CTL response seen in vivo.

In conclusion, the study by Inoue along with ours (1, 2) and other studies (3, 4) point to an important role for B cells in the modulation and shaping of antitumor response. These studies suggest that B cell depletion, using antibodies such as rituximab, may have a potential role in cancer immunotherapy and could be employed to further augment an antitumor response by T cells.

Inoue S, Leitner WW, Golding B, Scott D. Inhibitory effects of B cells on antitumor immunity.
Cancer Res
Shah S, Divekar AA, Hilchey SP, et al. Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and Th1 cytokine responses by B cells.
Int J Cancer
Mizoguchi A, Bhan AK. A case for regulatory B cells.
J Immunol
Burke F, Stagg AJ, Bedford PA, English N, Knight SC. IL-10-Producing B220+CD11c-APC in mouse spleen.
J Immunol