Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity
Pascal Meier1, Arnaud J Legrand2, Dieter Adam3
1The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London, UK. pascal.meier@icr.ac.uk.
Abstract:
Most metastatic cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by intratumour heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis - a largely immunologically silent form of cell death - there is growing interest in harnessing immunogenic forms of cell death such as necroptosis. Unlike apoptosis, necroptosis generates second messengers that act on immune cells in the tumour microenvironment, alerting them of danger. This lytic form of cell death optimizes the provision of antigens and adjuvanticity for immune cells, potentially boosting anticancer treatment approaches by combining cellular suicide and immune response approaches. In this Review, we discuss the mechanisms of necroptosis and how it activates antigen-presenting cells, drives cross-priming of CD8+ T cells and induces antitumour immune responses. We also examine the opportunities and potential drawbacks of such strategies for exposing cancer cells to immunological attacks.
Insights
Necroptosis, an immunogenic cell death, offers a promising strategy to overcome apoptosis-resistant cancers. By activating immune responses, it enhances cancer cell elimination and improves treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Cell Death Research
Background:
- Metastatic cancers are often incurable due to apoptosis-resistant cells.
- Current therapies primarily induce apoptosis, a non-immunogenic cell death.
- Intratumour heterogeneity and evolution contribute to treatment resistance.
Purpose of the Study:
- To review the mechanisms of necroptosis and its role in cancer therapy.
- To explore the potential of harnessing necroptosis for anticancer treatments.
- To examine the immunomodulatory effects of necroptosis in the tumour microenvironment.
Main Methods:
- Review of existing literature on necroptosis and cancer immunology.
- Analysis of necroptosis-induced immune cell activation and antigen presentation.
- Discussion of therapeutic strategies combining necroptosis with immunotherapy.
Main Results:
- Necroptosis, unlike apoptosis, generates danger signals that activate immune cells.
- It enhances antigen presentation and CD8+ T cell cross-priming.
- Necroptosis can induce potent antitumour immune responses.
Conclusions:
- Necroptosis represents a promising immunogenic cell death strategy for overcoming treatment resistance.
- Harnessing necroptosis offers opportunities to boost anticancer immunity.
- Potential drawbacks and challenges in clinical application require further investigation.
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