Sinister Self-Sacrifice: The Contribution of Apoptosis to Malignancy

Willems, Jorine J.L.P.; Arnold, Benjamin P.; Gregory, Christopher D.

doi:10.3389/fimmu.2014.00299

Cited by 20 publications

(16 citation statements)

References 45 publications

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“…These mediators orchestrate phagocyte recruitment and stimulate efferocytosis, but they also exert other pleiotropic effects [1,9]. Lactoferrin appears to be a promising candidate for an apoptotic-cell-derived trophic signal, since it can mediate multiple effects on living and dying tumor cells as well as on cells of the tumor microenvironment [10]; however, its functional involvement remains to be elucidated. Interestingly, apoptosis-mediated compensatory proliferation is only observed when apoptotic and viable cells are inoculated at the same site [8], implying that the responsible soluble factors display a rather limited operating range or that direct cell-cell contact is required.…”

Section: Kirsten Lauber 1 * and Martin Herrmannmentioning

confidence: 99%

Tumor Biology: With a Little Help from My Dying Friends

Lauber

Herrmann

2015

Current Biology

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Section: Kirsten Lauber 1 * and Martin Herrmannmentioning

confidence: 99%

Tumor Biology: With a Little Help from My Dying Friends

Lauber

Herrmann

2015

Current Biology

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“…Thus, it is not surprising that this huge number of apoptotic cells is normally cleared by phagocytosis without inflammatory reactions or tissue scarring. Apoptotic tumor cells might, therefore, also foster immune suppression [54]. Tumor cells can further secrete TGF-β or increase the expression of immune suppressive checkpoint molecules such as PD-L1 to make their microenvironment immunosuppressive; radiation even augments these effects [55][56][57].…”

Section: Immunosuppressive Effects By Radiationmentioning

confidence: 99%

Immune biological rationales for the design of combined radio- and immunotherapies

Häder

Frey

Fietkau

et al. 2020

Cancer Immunol Immunother

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Cancer immunotherapies are promising treatments for many forms of cancer. Nevertheless, the response rates to, e.g., immune checkpoint inhibitors (ICI), are still in low double-digit percentage. This calls for further therapy optimization that should take into account combination of immunotherapies with classical tumor therapies such as radiotherapy. By designing multimodal approaches, immune modulatory properties of certain radiation schemes, additional immune modulation by immunotherapy with ICI and hyperthermia, as well as patient stratification based on genetic and immune constitutions have to be considered. In this context, both the tumor and its microenvironment including cells of the innate and adaptive immune system have to be viewed in synopsis. Knowledge of immune activation and immune suppression by radiation is the basis for well-elaborated addition of certain immunotherapies. In this review, the focus is set on additional immune stimulation by hyperthermia and restoration of an immune response by ICI. The impact of radiation dose and fractionation on immune modulation in multimodal settings has to be considered, as the dynamics of the immune response and the timing between radiotherapy and immunotherapy. Another big challenge is the patient stratification that should be based on matrices of biomarkers, taking into account genetics, proteomics, radiomics, and "immunomics". One key aim is to turn immunological "cold" tumors into "hot" tumors, and to eliminate barriers of immune-suppressed or immune-excluded tumors. Comprehensive knowledge of immune alterations induced by radiation and immunotherapy when being applied together should be utilized for patient-adapted treatment planning and testing of innovative tumor therapies within clinical trials. Keywords Radioimmunotherapy • Hyperthermia • Immune checkpoint inhibitors • Tumor microenvironment • Personalized medicine • CITIM 2019 Abbreviations ATP Adenosine triphosphate ccRCC Clear cell renal cell carcinoma CT Chemotherapy CTLA-4 Cytotoxic T-lymphocyte associated protein 4 DAMPs Damage-associated molecular patterns

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“…Since UV-B induces a mixture of apoptotic and necrotic cells it would be worth to examine in the future how distinct forms of tumour cells death impact on the proliferation of viable tumour cells and what mixture But what are the radiation-induced trophic substances that stimulate tumour cell proliferation? Apoptotic cells release a variety of "find-me" signalling factors, including nucleotides, the lipid lysophosphatidylcholine (LPC) and proteins such as fractalkine (summarised in [118]). The latter mediates the chemotaxis of macrophages to apoptotic lymphocytes [119].…”

Section: Immune Suppressive and Proliferation Promoting Effects Of Ramentioning

confidence: 99%

“…RT-induced apoptosis may indeed lead to caspase 3-dependent tumour cell repopulation [46], but on the other hand caspase-3 is important to trigger immunogenic cancer cell death after hypofractionated irradiation [23]. Since TAM interacting with apoptotic tumour cells are central to activate multiple oncogenic pathways, to promote tumour cell growth and survival, angiogenesis, remodelling and metastasis [118] the aim should be to predominately induce necroptotic cancer cell death by RT [67,68] and to concurrently target TAM, e.g. by pharmacologic blockade of chemokine (C-X-C Motif) receptor 4 (CXCR4) [123].…”

Section: Immune Suppressive and Proliferation Promoting Effects Of Ramentioning

confidence: 99%

Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity

Frey

Derer

Scheithauer

et al. 2016

Apoptosis in Cancer Pathogenesis and Anti-Cancer Therapy

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Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence-associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies.

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Sinister Self-Sacrifice: The Contribution of Apoptosis to Malignancy

Cited by 20 publications

References 45 publications

Tumor Biology: With a Little Help from My Dying Friends

Tumor Biology: With a Little Help from My Dying Friends

Immune biological rationales for the design of combined radio- and immunotherapies

Cancer Cell Death-Inducing Radiotherapy: Impact on Local Tumour Control, Tumour Cell Proliferation and Induction of Systemic Anti-tumour Immunity

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