Cell-extrinsic effects of the tumor unfolded protein response on myeloid cells and T cells

Tumor‐infiltrating myeloid cells, macrophages, and dendritic cells (DCs) are key regulators of tumor immunity and growth. The origin of tumor‐derived signals that instruct myeloid cells in the tumor microenvironment is only partially understood. The endoplasmic reticulum (ER) stress response, or unf...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2013-05, Vol.1284 (1), p.6-11
Main Author: Zanetti, Maurizio
Format: Article
Language:English
Subjects:
Animals
arginase
Arginase - metabolism
CD8-Positive T-Lymphocytes - cytology
cross-priming
Cross-Priming - immunology
Cytokines - metabolism
dendritic cells
Dendritic Cells - cytology
Endoplasmic Reticulum - metabolism
ER stress
Humans
Immunology
Inflammation
Lymphocyte Activation - immunology
Macrophages - cytology
myeloid cells
Myeloid Cells - immunology
Neoplasms - immunology
Neoplasms - therapy
Phenotype
proinflammatory cytokines
Proteins
T-Lymphocytes - immunology
tumor growth facilitation
Tumor Microenvironment
Unfolded Protein Response
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Summary:Tumor‐infiltrating myeloid cells, macrophages, and dendritic cells (DCs) are key regulators of tumor immunity and growth. The origin of tumor‐derived signals that instruct myeloid cells in the tumor microenvironment is only partially understood. The endoplasmic reticulum (ER) stress response, or unfolded protein response (UPR), provides survival advantages to tumor growth. However, the cell‐extrinsic effects of the tumor UPR on immune cells have not been explored. Our laboratory recently showed that the tumor UPR can be transmitted by yet unidentified factor(s) to myeloid cells, macrophages, and DCs. ER stress transmission to receiver myeloid cells upregulates the production of proinflammatory cytokines, and contextually of arginase I, leading to a proinflammatory/suppressive phenotype. DCs imprinted by tumor‐borne ER stress transmissible factor(s) have decreased cross‐presentation of antigen and defective cross‐priming, causing T cell activation without proliferation. When DCs imprinted by transmissible ER stress are admixed with tumor cells and injected in vivo, facilitation of tumor growth is observed. Thus, tumor‐borne ER stress plays a hitherto unappreciated role at the tumor/immune interface that ultimately facilitates tumor growth.
ISSN:0077-8923
1749-6632
DOI:10.1111/nyas.12103