IL-1 Signaling in Tumor Microenvironment

Zhang, Weizhou; Borcherding, Nicholas; Kolb, Ryan

doi:10.1007/978-3-030-38315-2_1

Cited by 74 publications

(54 citation statements)

References 181 publications

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“…During the last decades, the role of IL-1 in the TME has been widely investigated [85][86][87]. IL-1 exerts its function modulating the composition of TME by recruiting MDSCs, TAM, TAN, Breg cells and Th17, and these subpopulations of immune cells are the source of IL-1 themselves.…”

Section: Discussionmentioning

confidence: 99%

Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Gelfo

Romaniello

Mazzeschi

et al. 2020

IJMS

104

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IL-1 belongs to a family of 11 members and is one of the seven receptor-agonists with pro-inflammatory activity. Beyond its biological role as a regulator of the innate immune response, IL-1 is involved in stress and chronic inflammation, therefore it is responsible for several pathological conditions. In particular, IL-1 is known to exert a critical function in malignancies, influencing the tumor microenvironment and promoting cancer initiation and progression. Thus, it orchestrates immunosuppression recruiting pro-tumor immune cells of myeloid origin. Furthermore, new recent findings showed that this cytokine can be directly produced by tumor cells in a positive feedback loop and contributes to the failure of targeted therapy. Activation of anti-apoptotic signaling pathways and senescence are some of the mechanisms recently proposed, but the role of IL-1 in tumor cells refractory to standard therapies needs to be further investigated.

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Section: Discussionmentioning

confidence: 99%

Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Gelfo

Romaniello

Mazzeschi

et al. 2020

IJMS

104

View full text Add to dashboard Cite

show abstract

“…Most of the protein up-regulated, including KLK14 and members of MAP kinase family, such as MAPK8 (JNK1) and MAPK14 (p38α), are implicated in the IL1 pathway. The expression of IL1R1 in tumor microenvironment, the main receptor of IL1α and b, due to the interconnection with NF-KB and MAP kinase pathways plays contrasting roles in different tumor stage [53]. Sustained PTGS2 (cox-2) expression con rmed pro-in ammatory pro le of NHF Onco-P20induced phenotype.…”

Section: Onco-p20 Deeply Modi Es Broblasts Gene and Protein Expressiomentioning

confidence: 98%

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: in vitro Evaluation in Non-Melanoma Skin Cancer

Bellei

Caputo

Migliano

et al. 2020

Preprint

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Abstract Background: Cancers are complex organs which encompass not only the tumor cells but also cells within the surrounding stroma. Such cells, mainly cancer associated fibroblasts (CAFs) and immune infiltrating cells, facilitate many aspects of cancer development providing a structural and supportive framework rich of bioactive compounds. So far, there are emerging studies proposing the combination of conventional anti-cancer therapy, directed against neoplastic cells, to molecules targeting tumor microenviroment. Methods: The study was designed to evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) on non-melanoma skin cancer (NMSC) and on the surronding dermal fibroblasts. This molecule, named Oncofid-P20 (Onco-P20), targets preferentially cells expressing high level of CD44, the natural ligand of HA.Results: Consistent with paclitaxel’s mechanism of action involving interferences with the normal breackdown of microtubules during cell division, highly sensible carcinoma cells underwent rapidly to apoptotic cell death. Interestingly, less sensible cells such as dermal fibroblasts resisted to the Onco-P20 treatment and experirenced a senescent-like status characterized by morphological change, decreaded proliferation, and significant modification of the gene espression profile. Onco-P20-treated fibroblasts lowered growth factors production, down-modulate Wnt signal pathway and acquired a pro-inflammatory profile. Independently to the direct exposure to taxol, in presence of Onco-P20-treated fibroblasts or their conditioned medium, carcinoma cells reduced the proliferation rate. Similar to NHF, fibroblasts isolated from skin cancer tumor lesion or from tissue adjacent to the tumor acquired an anti-neoplastic activity under Oncofid-P20 treatment.Conclusion: Collectively, our data demonstrated that Onco-P20, exerting both a direct and a NHF-mediated indirect paracrine effect on carcinoma cells, is a good candidate for an innovative therapy alternative to surgery for treatment of NMSC.

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“…Most of the protein up-regulated, including KLK14 and members of MAP kinase family, such as MAPK8 (JNK1) and MAPK14 (p38α), are implicated in the IL1 pathway. The expression of IL1R1 in tumor microenvironment, the main receptor of IL1α and β, due to the interconnection with NF-KB and MAP kinase pathways plays contrasting roles in different tumor stage [53]. Sustained PTGS2 (cox-2) expression con rmed pro-in ammatory pro le of NHF Onco-P20-induced phenotype.…”

Section: Onco-p20 Deeply Modi Es Broblasts Gene and Protein Expressiomentioning

confidence: 98%

Simultaneous targeting tumor cells and cancer-associated fibroblasts with a Paclitaxel-Hyaluronan bioconjugate: in vitro evaluation in non-melanoma skin cancer

Bellei

Caputo

Migliano

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Cancers are complex organs which encompass not only the tumor cells but also cells within the surrounding stroma. Such cells, mainly cancer associated fibroblasts (CAFs) and immune infiltrating cells, facilitate many aspects of cancer development providing a structural and supportive framework rich of bioactive compounds. So far, there are emerging studies proposing the combination of conventional anti-cancer therapy, directed against neoplastic cells, to molecules targeting tumor microenviroment.Methods: The study was designed to evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) on non-melanoma skin cancer (NMSC) and on the surronding dermal fibroblasts. This molecule, named Oncofid-P20 (Onco-P20), targets preferentially cells expressing high level of CD44, the natural ligand of HA.Results: Consistent with paclitaxel’s mechanism of action involving interferences with the normal breackdown of microtubules during cell division, highly sensible carcinoma cells underwent rapidly to apoptotic cell death. Interestingly, less sensible cells such as dermal fibroblasts resisted to the Onco-P20 treatment and experirenced a prologed growth arrest characterized by morphological change and significant modification of the gene espression profile that partially overlaps with that of senescent cells. Onco-P20-treated fibroblasts lowered growth factors production, down-modulate Wnt signal pathway and acquired a marked pro-inflammatory profile. Independently to the direct exposure to taxol, in presence of Onco-P20-treated fibroblasts or their conditioned medium, carcinoma cells reduced the proliferation rate. Similar to NHF, fibroblasts isolated from skin cancer tumor lesion or from tissue adjacent to the tumor acquired an anti-neoplastic activity under Oncofid-P20 treatment.Conclusion: Collectively, our data demonstrated that Onco-P20, exerting both a direct and a NHF-mediated indirect paracrine effect on carcinoma cells, is a good candidate for an innovative therapy alternative to surgery for treatment of NMSC.

show abstract

IL-1 Signaling in Tumor Microenvironment

Cited by 74 publications

References 181 publications

Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: in vitro Evaluation in Non-Melanoma Skin Cancer

Simultaneous targeting tumor cells and cancer-associated fibroblasts with a Paclitaxel-Hyaluronan bioconjugate: in vitro evaluation in non-melanoma skin cancer

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