Abstract
Based on the specificity of antigen recognition and the ability to generate long-lived memory responses, cancer immunotherapies primarily target tumor-associated T cells. Systemic administration of anti-IL-10R1 antibody in combination with local CpG administration has been shown to induce tumor regression in a T-cell-dependent manner. Here, we confirmed the anti-tumor efficacy of anti-IL-10R1 and CpG therapy in the highly aggressive B16F10 melanoma model. However, T cells were not required for tumor growth inhibition. Through cellular depletions and genetic models of leukocyte deficiency, we demonstrated that T, B, and NK cells, and neutrophils are not essential for anti-tumor efficacy. Nevertheless, hematopoietic cells as a whole are required for anti-IL-10R1- and CpG-induced tumor growth inhibition, suggesting that the collective action of multiple subsets of hematopoietic-derived cells is required for anti-tumor efficacy.
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Acknowledgments
We thank Andres Paler-Martinez for assistance with Luminex data, Wenjun Ouyang for providing il10r1 −/− mice, and Ira Mellman for scientific discussions. All authors are employees at Genentech, a member of the Roche Group. The authors declare no additional financial conflicts.
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Chou, MY., Austin, C.D. & Kim, J.M. Collective action of hematopoietic cell subsets mediates anti-IL10R1 and CpG tumor immunity. Cancer Immunol Immunother 61, 1055–1064 (2012). https://doi.org/10.1007/s00262-011-1175-3
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DOI: https://doi.org/10.1007/s00262-011-1175-3