Liu, Yang, Chen, Qingxin, Xu, Jiayu and Chi, Hao
2026.
Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.
Apoptosis
31
, 128.
10.1007/s10495-026-02298-y
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Abstract
Lung cancer remains the leading cause of cancer‐related mortality worldwide, with an estimated 2.2 million new cases and 1.8 million deaths in 2020. Despite improvements achieved through cytotoxic chemotherapy and immune checkpoint blockade, survival outcomes for many patients remain unsatisfactory, largely due to tumour immune-evasion and resistance to immunotherapy. In this context, programmed cell death (PCD) pathways—especially apoptosis, pyroptosis, ferroptosis and necroptosis—play central roles in shaping tumour cell fate, modulating the tumour immune microenvironment, and influencing therapeutic response. Apoptosis typically proceeds via caspase-mediated dismantling and is often immune-tolerogenic, whereas pyroptosis, ferroptosis and necroptosis provoke danger signals, inflammation and potent dendritic cell and T-cell activation, thus serving as immunogenic cell death modalities. Reciprocal crosstalk between these PCD types and the immune system determines whether lung tumours remain “cold” (immune‐excluded) or become “hot” (immune‐inflamed). Importantly, targeting these classical PCD mechanisms—either alone or in combination with immunotherapy—emerges as a promising strategy to overcome immune resistance in lung cancer by converting non-responsive tumours into immune-sensitive states. This review synthesises mechanistic insights into how apoptosis, pyroptosis, ferroptosis and necroptosis regulate antitumour immunity in lung cancer and outlines therapeutic opportunities for targeting PCD to enhance immunotherapy efficacy and overcome immune-resistant phenotypes.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Computer Science & Informatics |
| Additional Information: | RRS policy applied |
| Publisher: | Springer Verlag (Germany) |
| ISSN: | 1360-8185 |
| Date of First Compliant Deposit: | 28 April 2026 |
| Date of Acceptance: | 1 February 2026 |
| Last Modified: | 05 Aug 2026 12:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/186647 |
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