Immunogenic Cell Death in Cancer Therapy

Troitskaya, Olga; Novak, Diana; Richter, Vladimír; Koval, Olga

doi:10.32607/actanaturae.11523

Cited by 31 publications

(9 citation statements)

References 108 publications

(137 reference statements)

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“…Although extracellular HMGB1 is essential for the development of ICD-mediated immunogenicity, it is also associated with tumor progression. In recent years, ICD has emerged as a possible therapeutic approach for the development of novel therapeutics for the treatment of tumors, in which cytotoxic compounds promote both cancer cell death and the release of DAMP from dying cells [ 49 ]. These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells that clear out the neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

Role of HMGB1 in Cutaneous Melanoma: State of the Art

Pomi

Borgia

Custurone

et al. 2022

IJMS

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High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. It has already been studied in several diseases, among them melanoma. Indeed, HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. This research aims to assess the role of this molecule in the pathogenesis of human melanoma and its potential therapeutic role. The research has been conducted on the PubMed database, and the resulting articles are sorted by year of publication, showing an increasing interest in the last five years. The results showed that HMGB1 plays a crucial role in the pathogenesis of skin cancer, prognosis, and therapeutical response to therapy. Traditional therapies target this molecule indirectly, but future perspectives could include the development of new target therapy against HMGB1, thus adding a new approach to the therapy, which has often shown primary and secondary resistance. This could add a new therapy arm which has to be prolonged and specific for each patient.

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Section: Discussionmentioning

confidence: 99%

Role of HMGB1 in Cutaneous Melanoma: State of the Art

Pomi

Borgia

Custurone

et al. 2022

IJMS

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“…(Pawaria and Binder, 2011;Fucikova et al, 2021). The binding of ATP to its receptor also triggers the activation of cytotoxic T lymphocytes (CTLs), propels DC activation and maturation, and expands macrophage populations (Elliott et al, 2009;Troitskaya et al, 2022). The mechanism of ROS and ICD.…”

Section: Immunogenic Cell Deathmentioning

confidence: 99%

Exploiting cell death and tumor immunity in cancer therapy: challenges and future directions

Lu,

He,

Liu

et al. 2024

Front. Cell Dev. Biol.

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Cancer remains a significant global challenge, with escalating incidence rates and a substantial burden on healthcare systems worldwide. Herein, we present an in-depth exploration of the intricate interplay between cancer cell death pathways and tumor immunity within the tumor microenvironment (TME). We begin by elucidating the epidemiological landscape of cancer, highlighting its pervasive impact on premature mortality and the pronounced burden in regions such as Asia and Africa. Our analysis centers on the pivotal concept of immunogenic cell death (ICD), whereby cancer cells succumbing to specific stimuli undergo a transformation that elicits robust anti-tumor immune responses. We scrutinize the mechanisms underpinning ICD induction, emphasizing the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) as key triggers for dendritic cell (DC) activation and subsequent T cell priming. Moreover, we explore the contributions of non-apoptotic RCD pathways, including necroptosis, ferroptosis, and pyroptosis, to tumor immunity within the TME. Emerging evidence suggests that these alternative cell death modalities possess immunogenic properties and can synergize with conventional treatments to bolster anti-tumor immune responses. Furthermore, we discuss the therapeutic implications of targeting the TME for cancer treatment, highlighting strategies to harness immunogenic cell death and manipulate non-apoptotic cell death pathways for therapeutic benefit. By elucidating the intricate crosstalk between cancer cell death and immune modulation within the TME, this review aims to pave the way for the development of novel cancer therapies that exploit the interplay between cell death mechanisms and tumor immunity and overcome Challenges in the Development and implementation of Novel Therapies.

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“…In the TME, ATP acts on P2 purinergic receptors expressed on the surface of the tumor and host, and different ATP levels and types of P2 purinergic receptors have different effects ( 37 , 38 ). The ATP concentration required to activate P2X7 is greater than 100 μmol/L ( 39 ), and the P2X7 receptor can activate cytotoxic T lymphocytes. When the ATP concentration is less than 1 μmol/L ( 39 ), ATP can activate the P2Y2 receptor, and ATP acting on the P2Y2 receptor can send a “find me” signal to DCs and macrophages, promoting DC activation and maturation and the expansion of macrophages ( 40 ).…”

Section: Immunogenic Cell Deathmentioning

confidence: 99%

“…The ATP concentration required to activate P2X7 is greater than 100 μmol/L ( 39 ), and the P2X7 receptor can activate cytotoxic T lymphocytes. When the ATP concentration is less than 1 μmol/L ( 39 ), ATP can activate the P2Y2 receptor, and ATP acting on the P2Y2 receptor can send a “find me” signal to DCs and macrophages, promoting DC activation and maturation and the expansion of macrophages ( 40 ). Concurrently, lower concentrations of ATP can exert anti-inflammatory effects, mainly through activation of the NLRP3 inflammasome and massive release of proinflammatory cytokines, such as IL-1β and IL-18, mediating immunostimulatory effects ( 41 , 42 ).…”

Section: Immunogenic Cell Deathmentioning

confidence: 99%

Research progress in inducing immunogenic cell death of tumor cells

Xie

Wang

2022

Front. Immunol.

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Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combination of ICD inducers with other tumor treatments further enhances the immune response in tumor cells, and more tumor cells are killed; however, it also produces side effects of varying severity. New induction methods based on nanotechnology improve the antitumor ability and significantly reduces side effects because they can target tumor cells precisely. In this review, we introduce the characteristics and mechanisms of ICD responses in tumor cells and the DAMPs associated with ICD responses, summarize the current methods of inducing ICD response in tumor cells in five distinct categories: chemical sources, physical sources, pathogenic sources, combination therapies, and innovative therapies. At the same time, we introduce the limitations of current ICD inducers and make a summary of the use of ICD responses in clinical trials. Finally, we provide an outlook on the future of ICD inducer development and provide some constructive suggestions.

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Immunogenic Cell Death in Cancer Therapy

Cited by 31 publications

References 108 publications

Role of HMGB1 in Cutaneous Melanoma: State of the Art

Role of HMGB1 in Cutaneous Melanoma: State of the Art

Exploiting cell death and tumor immunity in cancer therapy: challenges and future directions

Research progress in inducing immunogenic cell death of tumor cells

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