Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy

被引:125
|
作者
Rapoport, Bernardo L. [1 ,2 ]
Anderson, Ronald [1 ,3 ]
机构
[1] Univ Pretoria, Dept Immunol, Fac Hlth Sci, ZA-0001 Pretoria, South Africa
[2] Med Oncol Ctr Rosebank, ZA-2196 Johannesburg, South Africa
[3] Univ Pretoria, Inst Cellular & Mol Med, Fac Hlth Sci, ZA-0001 Pretoria, South Africa
来源
关键词
calreticulin; damage-associated molecular patterns (DAMPs); dendritic cells; high mobility group box1; immunogenic cell death; immune checkpoint inhibitors; monoclonal antibodies; type I interferons; ANTITUMOR IMMUNITY; DNA-DAMAGE; T-CELLS; CALRETICULIN EXPOSURE; CROSS-PRESENTATION; DENDRITIC CELLS; LIGAND; TUMOR; INFLAMMATION; MECHANISMS;
D O I
10.3390/ijms20040959
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Immunogenic cell death (ICD), which is triggered by exposure of tumor cells to a limited range of anticancer drugs, radiotherapy, and photodynamic therapy, represents a recent innovation in the revitalized and burgeoning field of oncoimmunnotherapy. ICD results in the cellular redistribution and extracellular release of damage-associated molecular patterns (DAMPs), which have the potential to activate and restore tumor-targeted immune responses. Although a convincing body of evidence exists with respect to the antitumor efficacy of ICD in various experimental systems, especially murine models of experimental anticancer immunotherapy, evidence for the existence of ICD in the clinical setting is less compelling. Following overviews of hallmark developments, which have sparked the revival of interest in the field of oncoimmunotherapy, types of tumor cell death and the various DAMPs most prominently involved in the activation of antitumor immune responses, the remainder of this review is focused on strategies which may potentiate ICD in the clinical setting. These include identification of tumor- and host-related factors predictive of the efficacy of ICD, the clinical utility of combinatorial immunotherapeutic strategies, novel small molecule inducers of ICD, novel and repurposed small molecule immunostimulants, as well as the critical requirement for validated biomarkers in predicting the efficacy of ICD.
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页数:27
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