Prognostic and Predictive Value of DAMPs and DAMP-Associated Processes in Cancer

Abstract

It is now clear that human neoplasms form, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (re)activation of tumor-targeting immune responses. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents, and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as “immunogenic cell death.” Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as “damage-associated molecular patterns” (DAMPs), may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.

The mitochondrial dynamics in cancer and immune-surveillance

“…Innate immune cells, such as dendritic cells (DCs), natural killer T (NKT) cells and macrophages, recognize DAMPs through pattern-recognition-receptors (PRRs) [171,172]. Once activated, these cells can directly kill the tumor cells in the TME or can migrate toward secondary lymphoid organs, where they activate cytotoxic CD8+ T cells of the adaptive immune response, which later migrate into the tumor mass recalled by local cytokines.…”

Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

“…CD, cluster of differentiation Table 2 summarizes the prognostic or predictive impact of major phagocytic determinants, among which CRT/CALR and CD47 are the most studied (Table 2). High expression of CD47 is a definitive negative prognostic factor across various cancer types (Table 2), 106 whereas the overall picture is much more complex for ecto-CRT/CALR. 106 Increased ecto-CRT or high CALR levels predict positive responses to immunogenic anticancer therapies, such as anthracyclines, radiotherapy, paclitaxel and DC vaccines ( Table 2).…”

“…High expression of CD47 is a definitive negative prognostic factor across various cancer types (Table 2), 106 whereas the overall picture is much more complex for ecto-CRT/CALR. 106 Increased ecto-CRT or high CALR levels predict positive responses to immunogenic anticancer therapies, such as anthracyclines, radiotherapy, paclitaxel and DC vaccines ( Table 2). 106 However, as a prognostic factor the utility of CALR is limited to only a few cancer types.…”

“…106 Increased ecto-CRT or high CALR levels predict positive responses to immunogenic anticancer therapies, such as anthracyclines, radiotherapy, paclitaxel and DC vaccines ( Table 2). 106 However, as a prognostic factor the utility of CALR is limited to only a few cancer types. 90 This discrepancy could be because of differences in phagocytic context.…”

Radio-Immunotherapy: A Promising Weapon to Consider in the Fight against NSCLC

“…Also, these proteins can be released as cytokines. 14 The nuclear High Mobility Group Box 1 protein (HMGB1) and ATP are also released from the dying cell and recognized by de APC. 12 The final effects of these pathways lead to an improved uptake of tumor cells and recognition of tumor-derived antigens.…”