Therapeutic Strategies for Targeting IL-1 in Cancer

Gottschlich, Adrian; Endres, Stefan; Kobold, Sebastian

doi:10.3390/cancers13030477

Cited by 35 publications

(33 citation statements)

References 104 publications

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“…39 Anti-IL1B mAb canakinumab has been now clinically evaluated in combination with immunotherapy or chemotherapy for treating various types of cancers, including lung cancer, pancreatic cancer, and renal cancer. 40 Usually, anti-PD1 mAb is the first choice as an immunotherapeutic in combination with other drugs despite many failures in the clinical trials. 16 However, blocking PD1 is likely helpless in the treatment of metastatic CRC, since almost no differences of PD1 + T cells in PBMCs were observed between healthy donors and patients with CRC (figure 5A), and blocking PD1 may be ineffective in suppressing tumor promotion via the TAMy-caused lipidization.…”

Section: Discussionmentioning

confidence: 99%

CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer

Imazeki

Ogiwara²,

Kawamura³

et al. 2021

J Immunother Cancer

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BackgroundTumor metastasis is the major cause of death of colorectal cancer (CRC), and metastatic CRC remains incurable in many cases despite great advances in genetic and molecular profiling, and clinical development of numerous drugs, including immune checkpoint inhibitors. Thus, more effective treatments are urgently needed for the patients in clinical settings.MethodsWe used mouse CRC metastasis models that murine Colon26 cells were subcutaneously and intravenously implanted and attempted to elucidate the tumor biological and immunological mechanisms underlying cancer metastasis. Then, we evaluated in vivo antitumor efficacy induced by agents targeting the identified molecular mechanisms using the mouse models. We validated the clinical relevancy of the findings using peripheral blood mononuclear cells obtained from stage IV metastatic CRC patients.ResultsCD11b+CTLA4+ myeloid cells were systemically expanded in the metastatic settings and facilitated tumor progression and metastasis directly via generating lipid droplets in tumor cells and indirectly via inducing immune exhaustion. These events were mediated by IL1B produced via the CTLA4 signaling from the increased myeloid cells. Blocking CTLA4 and IL1B with the specific mAbs significantly suppressed tumor progression and metastasis in the mouse models resistant to anti-PD1 therapy, and the therapeutic efficacy was optimized by blocking cyclooxygenases with aspirin.ConclusionsThe CD11b+CTLA4+ cells are a key driver of tumor evasion, and targeting the CTLA4-IL1B axis could be a promising strategy for treating metastatic CRC. The triple combination regimen with anti-CTLA4/IL1B mAbs and aspirin may be useful in clinical settings.

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Section: Discussionmentioning

confidence: 99%

CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer

Imazeki

Ogiwara²,

Kawamura³

et al. 2021

J Immunother Cancer

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“…IL-1, for example, is a downstream effector of Ras activation and NF-κB regulatory gene activation, which is necessary to provide a favorable microenvironment for tumor formation [ 105 ]. A recent second phase of a clinical trial of a recombinant IL-1R antagonist for multiple myeloma has shown a favorable safety profile and reduced morbidity, demonstrating that anti-IL-1 therapy is a viable cancer treatment option [ 106 ]. BBR inhibits the inflammatory cytokine caspase-1 activation through ERK1/2 signaling as well as glioma cells’ subsequent development of IL-1 and IL-18.…”

Section: Anticancer Perspectivesmentioning

confidence: 99%

Berberine as a Potential Anticancer Agent: A Comprehensive Review

et al. 2021

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Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial–mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.

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“…Inflammation also plays a role in the development and progression of cancer ( 30 , 31 ). IL-1 has been shown to mediate tumor angiogenesis, metastasis, and tumor immune evasion ( 32 , 33 ). IL-1 initiates and amplifies inflammation and can be produced by both immune (myeloid cells, macrophages, etc) and nonimmune cells in response to danger-associated molecular patterns and pathogen-associated molecular patterns ( 34 ).…”

Section: An Inflammatory Common Link Among Atherosclerosis Af and Cancermentioning

confidence: 99%

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

Leiva

AbdelHameid

Connors

et al. 2021

JACC: CardioOncology

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Cardiovascular disease and cancer are the 2 leading causes of death worldwide. Emerging evidence suggests common mechanisms between cancer and cardiovascular disease, including atrial fibrillation and atherosclerosis. With advances in cancer therapies, screening, and diagnostics, cancer-specific survival and outcomes have improved. This increase in survival has led to the coincidence of cardiovascular disease, including atrial fibrillation and atherosclerosis, as patients with cancer live longer. Additionally, cancer and cardiovascular disease share several risk factors and underlying pathophysiologic mechanisms, including inflammation, cancer-related factors including treatment effects, and alterations in platelet function. Patients with cancer are at increased risk for bleeding and thrombosis compared with the general population. Although optimal antithrombotic therapy, including agent choice and duration, has been extensively studied in the general population, this area remains understudied in patients with cancer despite their altered thrombotic and bleeding risk. Future investigation, including incorporation of cancer-specific characteristics to traditional thrombotic and bleeding risk scores, clinical trials in the cancer population, and the development of novel antithrombotic and anti-inflammatory strategies on the basis of shared pathophysiologic mechanisms, is warranted to improve outcomes in this patient population.

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Therapeutic Strategies for Targeting IL-1 in Cancer

Cited by 35 publications

References 104 publications

CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer

CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer

Berberine as a Potential Anticancer Agent: A Comprehensive Review

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

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Therapeutic Strategies for Targeting IL-1 in Cancer

Cited by 35 publications

References 104 publications

CD11b+CTLA4+myeloid cells are a key driver of tumor evasion in colorectal cancer

CD11b+CTLA4+myeloid cells are a key driver of tumor evasion in colorectal cancer

Berberine as a Potential Anticancer Agent: A Comprehensive Review

Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis

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CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer

CD11b⁺CTLA4⁺myeloid cells are a key driver of tumor evasion in colorectal cancer