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

Fucikova J, Moserova I, Urbanova L, Bezu L, Kepp O, Cremer I, Salek C, Strnad P, Kroemer G, Galluzzi L, Spisek R - Front Immunol (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Sotio , Prague , Czech Republic ; Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University , Prague , Czech Republic.

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.

No MeSH data available.


Related in: MedlinePlus

Prognostic and predictive value of DAMPs and DAMP-associated processes. (A,B). Monitoring the emission of damage-associated molecular patterns (DAMPs) or DAMP-associated processes may have a multifaceted impact on the clinical management of cancer patients. First, it may allow for a prognostic assessment and permit the stratification of patients in different risk groups (A). Second, it may allow for the identification of patients who are intrinsically capable or uncapable to respond to a specific treatment, and amongst the latter, those who may benefit from combinatorial therapeutic approaches aimed at restoring normal DAMP signaling (B).
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Figure 1: Prognostic and predictive value of DAMPs and DAMP-associated processes. (A,B). Monitoring the emission of damage-associated molecular patterns (DAMPs) or DAMP-associated processes may have a multifaceted impact on the clinical management of cancer patients. First, it may allow for a prognostic assessment and permit the stratification of patients in different risk groups (A). Second, it may allow for the identification of patients who are intrinsically capable or uncapable to respond to a specific treatment, and amongst the latter, those who may benefit from combinatorial therapeutic approaches aimed at restoring normal DAMP signaling (B).

Mentions: It is now clear that the emission of DAMPs according to a specific spatiotemporal pattern is an absolute requirement for the elicitation of immune responses against malignant cells succumbing to treatment, and that such responses are necessary for the full-blown efficacy of most (if not all) anticancer therapeutic regimens. In many settings, however, neoplastic cells exposed to conventional chemotherapeutics, radiotherapy or targeted anticancer agents fail to emit DAMPs in a manner compatible with the activation of the immune system, calling for the development of complementation strategies (16). Several approaches are being conceived to address this issue, including the implementation of combinatorial therapeutic regimens including (1) ER stressors, recombinant CALR or recombinant HSPs, to complement for defects in the CALR or HSP exposure pathway; (2) TLR3 agonists or recombinant type I IFNs, to correct problems in the secretion of type I IFN; (3) autophagy inducers or inhibitors of extracellular ATP-degrading enzymes, to maximize the amount of ATP secreted in the course of cell death; and (4) recombinant HMGB1, TLR4 agonists or cytotoxic agents, to restore HMGB1-dependent immunostimulation (225). Besides, consistent efforts are being devoted to the identification of additional strategies that per se induce ICD, in vivo (with direct therapeutic purposes), and in vitro (for instance, for the development of anticancer vaccines) (20). Monitoring DAMPs and DAMP-associated processes may therefore have a dual clinical relevance (Figure 1). First, it may improve patient stratification by allowing for the identification of individuals with different prognosis and/or subjects who are likely to respond (or are responding) to a particular therapeutic regimen. Second, it may instruct therapeutic choices by spotting specific molecular or cellular defects that may be corrected pharmacologically. We surmise that the prognostic and/or predictive value of DAMPs and DAMP-associated processes will have a significant impact on the clinical management of cancer patients.


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

Fucikova J, Moserova I, Urbanova L, Bezu L, Kepp O, Cremer I, Salek C, Strnad P, Kroemer G, Galluzzi L, Spisek R - Front Immunol (2015)

Prognostic and predictive value of DAMPs and DAMP-associated processes. (A,B). Monitoring the emission of damage-associated molecular patterns (DAMPs) or DAMP-associated processes may have a multifaceted impact on the clinical management of cancer patients. First, it may allow for a prognostic assessment and permit the stratification of patients in different risk groups (A). Second, it may allow for the identification of patients who are intrinsically capable or uncapable to respond to a specific treatment, and amongst the latter, those who may benefit from combinatorial therapeutic approaches aimed at restoring normal DAMP signaling (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528281&req=5

Figure 1: Prognostic and predictive value of DAMPs and DAMP-associated processes. (A,B). Monitoring the emission of damage-associated molecular patterns (DAMPs) or DAMP-associated processes may have a multifaceted impact on the clinical management of cancer patients. First, it may allow for a prognostic assessment and permit the stratification of patients in different risk groups (A). Second, it may allow for the identification of patients who are intrinsically capable or uncapable to respond to a specific treatment, and amongst the latter, those who may benefit from combinatorial therapeutic approaches aimed at restoring normal DAMP signaling (B).
Mentions: It is now clear that the emission of DAMPs according to a specific spatiotemporal pattern is an absolute requirement for the elicitation of immune responses against malignant cells succumbing to treatment, and that such responses are necessary for the full-blown efficacy of most (if not all) anticancer therapeutic regimens. In many settings, however, neoplastic cells exposed to conventional chemotherapeutics, radiotherapy or targeted anticancer agents fail to emit DAMPs in a manner compatible with the activation of the immune system, calling for the development of complementation strategies (16). Several approaches are being conceived to address this issue, including the implementation of combinatorial therapeutic regimens including (1) ER stressors, recombinant CALR or recombinant HSPs, to complement for defects in the CALR or HSP exposure pathway; (2) TLR3 agonists or recombinant type I IFNs, to correct problems in the secretion of type I IFN; (3) autophagy inducers or inhibitors of extracellular ATP-degrading enzymes, to maximize the amount of ATP secreted in the course of cell death; and (4) recombinant HMGB1, TLR4 agonists or cytotoxic agents, to restore HMGB1-dependent immunostimulation (225). Besides, consistent efforts are being devoted to the identification of additional strategies that per se induce ICD, in vivo (with direct therapeutic purposes), and in vitro (for instance, for the development of anticancer vaccines) (20). Monitoring DAMPs and DAMP-associated processes may therefore have a dual clinical relevance (Figure 1). First, it may improve patient stratification by allowing for the identification of individuals with different prognosis and/or subjects who are likely to respond (or are responding) to a particular therapeutic regimen. Second, it may instruct therapeutic choices by spotting specific molecular or cellular defects that may be corrected pharmacologically. We surmise that the prognostic and/or predictive value of DAMPs and DAMP-associated processes will have a significant impact on the clinical management of cancer patients.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Sotio , Prague , Czech Republic ; Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University , Prague , Czech Republic.

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.

No MeSH data available.


Related in: MedlinePlus