Abstract
Immunogenic Cell Death (ICD) could represent the keystone in cancer management since tumor cell death induction is crucial as well as the control of cancer cells revival after neoplastic treatment. In this context, the immune system plays a fundamental role. The concept of Damage-Associated Molecular Patterns (DAMPs) has been proposed to explain the immunogenic potential of stressed or dying/dead cells. ICD relies on DAMPs released by or exposed on dying cells. Once released, DAMPs are sensed by immune cells, in particular Dendritic Cells (DCs), acting as activators of Antigen-Presenting Cells (APCs), that in turn stimulate both innate and adaptive immunity. On the other hand, by exposing DAMPs, dying cancer cells change their surface composition, recently indicated as vital for the stimulation of the host immune system and the control of residual ill cells. It is well established that PhotoDynamic Therapy (PDT) for cancer treatment ignites the immune system to elicit a specific antitumor immunity, probably linked to its ability in inducing exposure/release of certain DAMPs, as recently suggested. In the present paper, we discuss the DAMPs associated with PDT and their role in the crossroad between cancer cell death and immunogenicity in PDT.
Highlights
E plain success of cancer therapies crucially depends on the synergic interaction between immune cells and dying/dead cancer cells. e ideal cancer treatment should merge the direct cytotoxic action on tumor cells with potent immunostimulatory effects based on the recognition of molecular immunogenic determinants on dying cells by immune cells
Anticancer immune responses may contribute to the control of the neoplastic disease a er cancer modalities since they help to eliminate residual cancer cells or maintain micrometastases in a stage of dormancy. e capability of a cancer treatment to elicit Immunogenic Cell Death is clinically relevant since it is associated with an anticancer immune response that reinforces the therapeutic effect of the therapy. e immunogenicity of the dying cancer cells involves subtle changes in their surface proteome and the secretion of soluble molecules known as Damage-Associated Molecular Patterns (DAMPs) allowing their immunogenic recognition by immune effectors
Unlike normal cells whose growth is kept under control by inhibitors in the surrounding environment, in the extracellular matrix and on the surface of neighboring cells, tumor cells are generally resistant to growth-preventing signals becoming masters of their own destinies. ey are able to bypass apoptosis, the preferential form of Programmed Cell Death (PCD) induced by conventional cancer therapies, by the loss of Tumor Protein 53 (TP53) tumor suppressor function, the upregulation of antiapoptotic regulators (Bcl-2, Bcl-xL) or of survival signals (Igf1/2), the downregulation of proapoptotic factors (Bax, Bim, Puma), or the short-circuiting of the extrinsic ligand-induced death pathway
Summary
E plain success of cancer therapies crucially depends on the synergic interaction between immune cells and dying/dead cancer cells. e ideal cancer treatment should merge the direct cytotoxic action on tumor cells with potent immunostimulatory effects based on the recognition of molecular immunogenic determinants on dying cells by immune cells. E capability of a cancer treatment to elicit Immunogenic Cell Death is clinically relevant since it is associated with an anticancer immune response that reinforces the therapeutic effect of the therapy. E immunogenicity of the dying cancer cells involves subtle changes in their surface proteome and the secretion of soluble molecules known as Damage-Associated Molecular Patterns (DAMPs) allowing their immunogenic recognition by immune effectors. More and more efforts are addressed to associate particular DAMPs with a speci c cell death pathway or with particular stress agents able to induce Immunogenic Cell Death (ICD) in cancer cells. One such therapeutic modality certainly associated with DAMPs is PhotoDynamic erapy (PDT). We collect data regarding DAMPs related to PDT, primarily focusing on the ability of these molecules to function as ICD effectors in PDT
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