Nature immunology Eosinophils orchestrate cancer rejection by normalizing
Nature immunology Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD 8+ T cells Huang Jie Wen
Background l Tumor-associated eosinophilia is frequently observed in cancer. l 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 CD 8+ 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 M 1 -like polarization of tumor-associated macrophages.
DISCUSSION l In the present study we have addressed this longstanding question and propose a new concept for eosinophils in cancer. l We found that eosinophils served as critical accessory cells for the attraction of tumor-specific CD 8+ T cells. Activated tumor-infiltrating eosinophils produced large amounts of chemokines, such as CCL 5, CXCL 9 and CXCL 10, that recruited co-transferred CD 8+T cells to the tumor, which resulted in tumor rejection and prolonged survival.
l 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. l Eosinophils might now emerge as a promising tool for the improvement of clinical cancer immunotherapy.
l. Thank you!
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