Interference of immunogenic chemotherapy by artificially controlled calreticulin secretion from tumor cells

Liwei Zhao, Shuai Zhang, Hui Chen, Guido Kroemer, Oliver Kepp, Peng Liu

    Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

    2 Citations (Scopus)

    Abstract

    The exposure of calreticulin (CALR) on the cell surface of apoptotic cancer cells is an important “eat-me” signal that stimulates the engulfment by antigen presenting cells (APCs). When cells are exposed to immunogenic cell death (ICD) inducers, CALR translocates from the lumen of the endoplasmic reticulum (ER) to the cell surface, where it serves as a ligand for LDL-receptor-related protein 1 (LRP1, also known as CD91) expressed by dendritic cells (DCs). Surface-exposed CALR facilitates tumor antigen transfer to DCs and in turn antigen cross-presentation to cytotoxic T cells, altogether culminating in the activation of adaptive immune responses. Consistent with its role as an apical signaling event in anticancer immunity, blocking or neutralizing CALR abolishes the immune-dependent anticancer efficacy of a variety of ICD inducing anticancer agents. Recently we showed that saturating CALR receptors on DCs with abundant recombinant CALR protein, or soluble CALR secreted from cancer cells decreases the potency of ICD-mediated antitumor immune responses. Here we detail how to harness an artificially inducible release of soluble CALR from engineered cancer cells, which can blind DCs from recognizing immunogenic cancer cells, resulting in reduced anticancer immunity. This system offers precise control over the release of immunosuppressive soluble CALR, thus yielding a useful tool for the validation of ICD-inducing immunotherapies.

    Original languageEnglish
    Title of host publicationRadiation Oncology and Radiotherapy Part A
    EditorsAi Sato, Jeffrey Kraynak, Ariel E. Marciscano, Lorenzo Galluzzi
    PublisherAcademic Press Inc.
    Pages99-114
    Number of pages16
    ISBN (Print)9780323899499
    DOIs
    Publication statusPublished - 1 Jan 2022

    Publication series

    NameMethods in Cell Biology
    Volume172
    ISSN (Print)0091-679X

    Keywords

    • DAMPs
    • Immunosuppression
    • Immunotherapy
    • RUSH

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