Detection of immunogenic cell death and its relevance for cancer therapy
Jitka Fucikova1,2, Oliver Kepp3,4, Lenka Kasikova1,2
1Sotio, Prague, Czech Republic.
Abstract:
Chemotherapy, radiation therapy, as well as targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which altogether confer a robust adjuvanticity to dying cancer cells, as they favor the recruitment and activation of antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) as well as secreted ATP, annexin A1 (ANXA1), type I interferon, and high-mobility group box 1 (HMGB1). Additional hallmarks of ICD encompass the phosphorylation of eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known as eIF2α), the activation of autophagy, and a global arrest in transcription and translation. Here, we outline methodological approaches for measuring ICD markers in vitro and ex vivo for the discovery of next-generation antineoplastic agents, the development of personalized anticancer regimens, and the identification of optimal therapeutic combinations for the clinical management of cancer.
Insights
Cancer therapies can trigger immune responses by inducing immunogenic cell death (ICD). Measuring ICD markers helps discover new anticancer drugs and personalize cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Anticancer therapies like chemotherapy and radiation can elicit anti-tumor immune responses.
- These responses depend on cancer cell antigenicity and adjuvant signals, particularly from immunogenic cell death (ICD).
- ICD involves the release of damage-associated molecular patterns (DAMPs) that enhance antigen presentation and immune cell activation.
Purpose of the Study:
- To outline methods for measuring ICD markers in vitro and ex vivo.
- To support the discovery of novel anticancer agents.
- To aid in developing personalized cancer treatment regimens and optimizing therapeutic combinations.
Main Methods:
- Measurement of surface-exposed calreticulin (CALR).
- Quantification of secreted ATP, annexin A1 (ANXA1), type I interferon, and high-mobility group box 1 (HMGB1).
- Assessment of eukaryotic translation initiation factor 2 subunit-α (EIF2S1) phosphorylation, autophagy activation, and transcription/translation arrest.
Main Results:
- Established methodological approaches for quantifying key ICD markers.
- Demonstrated the role of DAMPs in recruiting and activating antigen-presenting cells.
- Highlighted specific molecular events characterizing ICD, including eIF2α phosphorylation and autophagy.
Conclusions:
- Accurate measurement of ICD markers is crucial for advancing cancer therapy.
- These methods facilitate the discovery of next-generation antineoplastic agents.
- The findings support personalized medicine and optimized combination therapies for cancer management.
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