Nature immunology Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells Huang Jie Wen

Background Tumor-associated eosinophilia is frequently observed in cancer. However, despite numerous studies of patients with cancer and mouse models of cancer, it has remained uncertain if eosinophils contribute to tumor immunity or are mere bystander cells.

Figure 1: Treg cell depletion results in eosinophil infiltration and tumor rejection.

Figure 2: Tumor rejection after Treg cell depletion is dependent on infiltrating eosinophils.

Figure 3: Changes in the tumor microenvironment after depletion of Treg cells and eosinophils.

Figure 4: Eosinophil-derived chemokines induce T cell migration and vascular normalization.

Figure 5: Adoptive transfer of tumor-specific CD8+ T cells alone fails to reject tumors, whereas transfer of those cells together with activated eosinophils leads to substantial T cell infiltration and tumor rejection

Figure 6: Cotransfer of cells promotes a reduction in vessel size and increases VCAM-1 expression.

Figure 7: Normalization of tumor vasculature

Figure 8: Cotransfer of cells results in the M1-like polarization of tumor-associated macrophages.

DISCUSSION In the present study we have addressed this long-standing question and propose a new concept for eosinophils in cancer. We found that eosinophils served as critical accessory cells for the attraction of tumor-specific CD8+ T cells. Activated tumor-infiltrating eosinophils produced large amounts of chemokines, such as CCL5, CXCL9 and CXCL10, that recruited co-transferred CD8+T cells to the tumor, which resulted in tumor rejection and prolonged survival.

Co-transfer of eosinophils and T cells led also to considerable changes in the tumor microenvironment, including normalization of the tumor vasculature and macrophage polarization. Eosinophils might now emerge as a promising tool for the improvement of clinical cancer immunotherapy.

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