Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Dalil Hannani (1) , C. Locher (1) , T Yamazaki (1) , V Colin-Minard (2) , M Vetizou (1) , L Aymeric (1) , S. Viaud (1) , D Sanchez (3) , M. Smyth (4) , Pierre Bruhns (5) , G. Kroemer (6) , L. Zitvogel (1, 7)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 IGR - Institut Gustave Roussy
3 MBU / CAS - Institute of Microbiology of the Czech Academy of Sciences [Prague, Czech Republic]
4 USQ - University of Southern Queensland
5 Anticorps en Thérapie et Pathologie
6 U848 - Apoptose, cancer et immunité
7 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers

Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-cell-depleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

Domaines: Immunothérapie; Immunologie; Cancer

Dalil Hannani, C. Locher, T Yamazaki, V Colin-Minard, M Vetizou, et al.. Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines. Cell Death and Differentiation, 2014, 21 (1), pp.50-58. ⟨10.1038/cdd.2013.60⟩. ⟨hal-02047412⟩