Inflammatory Cytokines in Cancer: Comprehensive Understanding and Clinical Progress in Gene Therapy

Lan, Tu; Chen, Li; Wei, Xiawei

doi:10.3390/cells10010100

Cited by 150 publications

(112 citation statements)

References 111 publications

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“…While chronic inflammation results in a predisposition to the development of specific cancers, cancer-related inflammation generally affects all aspects of malignancies, including proliferation and survival of malignant cells, angiogenesis, and metastasis [1][2][3]. Immune cell infiltration is observed in almost all tumours, ranging from subtle infiltrations detectable by only cell-type specific antibodies to gross accumulations of lymphocytes, macrophages, or mast cells [1][2][3]. These cell infiltrates secrete a repertoire of inflammatory proteins such as cytokines, which serve as important orchestrators of cancer-inflammation interactions.…”

Section: Introductionmentioning

confidence: 99%

Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients

Winter

Hotterbeekx

Huizing

et al. 2021

Cancers

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Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-β, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

show abstract

Section: Introductionmentioning

confidence: 99%

Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients

Winter

Hotterbeekx

Huizing

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…While chronic inflammation predisposes to development of specific cancers, cancer-related inflammation generally affects all aspects of malignancies, including proliferation and survival of malignant cells, angiogenesis, and metastasis [1][2][3]. Immune cell infiltration is observed in almost all tumours, ranging from subtle infiltrations detectable by only celltype specific antibodies to gross accumulations of lymphocytes, macrophages, or mast cells [1][2][3]. These cell infiltrates secrete a repertoire of inflammatory proteins such as cytokines that serve as important orchestrators of cancer-inflammation interactions.…”

Section: Introductionmentioning

confidence: 99%

“…However, paradoxically, many cytokines support chronic inflammation thereby promoting tumour growth and influence multiple aspects of cancer metastasis. Examples of such tumour promoting cytokines are IL-6, Tumour necrosis factor α (TNF-) and Transforming growth factor  (TGF-), where several clinical trials targeting these cancer-promoting cytokines are ongoing [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Blood cytokine analysis suggests that SARS-CoV-2 infection results in a sustained tumour promoting environment in cancer patients

Winter

Hotterbeekx

Huizing

et al. 2021

Preprint

View full text Add to dashboard Cite

Cytokines, chemokines and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n=54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n=42). Of the 35 CCGs, 19 were common to both solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n=52). Of these TNF-α, IFN-β, TSLP and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data urge for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

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“…In malignancies including GBMs, the tissue repairing cascade fails to resolve the trauma, and chronic inflammation develops. The state of chronic inflammation invokes leukocytes to secrete mitogenic growth mediators in abundance, inducing a proliferation of cancer and stromal cells [22,26]. Now, we will discuss the role of proinflammatory molecules in GBM development.…”

Section: Molecular Mechanism Of Neuroinflammationmentioning

confidence: 99%

Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

Basheer

Abas

Othman

et al. 2021

Cancers

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Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.

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Inflammatory Cytokines in Cancer: Comprehensive Understanding and Clinical Progress in Gene Therapy

Cited by 150 publications

References 111 publications

Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients

Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients

Blood cytokine analysis suggests that SARS-CoV-2 infection results in a sustained tumour promoting environment in cancer patients

Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

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