IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D

Kiss, Máté; Walle, Lieselotte Vande; Saavedra, Pedro; Lebegge, Els; Damme, Helena Van; Murgaski, Aleksandar; Qian, Jun; Ehling, Manuel; Pretto, Samantha; Bolli, Evangelia; Keirsse, Jiri; Bardet, Pauline M. R.; Arnouk, Sana M.; Elkrim, Yvon; Schmoetten, Maryse; Brughmans, Jan; Debraekeleer, Ayla; Fossoul, Amelie; Boon, Louis; Raes, Geert; Loo, Geert; Lambrechts, Diether; Mazzone, Massimiliano; Beschin, Alain; Wullaert, Andy; Lamkanfi, Mohamed; Ginderachter, Jo A. Van; Laoui, Damya

doi:10.1158/2326-6066.cir-20-0431

Cited by 52 publications

(28 citation statements)

References 60 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study suggests that specific depletion of the CD163+ macrophages can trigger tumor shrinkage in a melanoma model by increasing infiltration of effector T cells and concomitant recruitment of pro-inflammatory TAMs ( 158 ). Likewise, it is implied that IL-1β contributes to an immunosuppressive TME and favors tumor growth; inhibition of IL1β drives the accumulation of CD8 + T cells at tumor sites, which subsequently activates TAMs and induces tumor regression; nevertheless, depletion of TAMs with CSF-1R inhibitor can abolish tumor shrinkage caused by IL-1β deficient ( 159 ). These findings suggest that macrophage-T cell cross-talk plays an important role in the anti-tumor immune response.…”

Section: Therapeutic Strategies Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

et al. 2021

View full text Add to dashboard Cite

Macrophages, an important class of innate immune cells that maintain body homeostasis and ward off foreign pathogens, exhibit a high degree of plasticity and play a supportive role in different tissues and organs. Thus, dysfunction of macrophages may contribute to advancement of several diseases, including cancer. Macrophages within the tumor microenvironment are known as tumor-associated macrophages (TAMs), which typically promote cancer cell initiation and proliferation, accelerate angiogenesis, and tame anti-tumor immunity to promote tumor progression and metastasis. Massive infiltration of TAMs or enrichment of TAM-related markers usually indicates cancer progression and a poor prognosis, and consequently tumor immunotherapies targeting TAMs have gained significant attention. Here, we review the interaction between TAMs and cancer cells, discuss the origin, differentiation and phenotype of TAMs, and highlight the role of TAMs in pro-cancer functions such as tumor initiation and development, invasive metastasis, and immunosuppression. Finally, we review therapies targeting TAMs, which are very promising therapeutic strategies for malignant tumors.

show abstract

Section: Therapeutic Strategies Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Meanwhile, in the treatment of cancer, various drugs could induce the activation of inflammasome-related pyroptosis and cause the release of proinflammatory cytokines. Subsequently, the activated inflammatory cytokines could recruit the NK or cytotoxic T cells to the tumor site for killing cancer cells, and eventually delay the tumor progression ( 108 , 109 ).…”

Section: Pyroptotic Inflammasome Signaling Acts As a Critical Regulator Of Inflammation And Tils Within Tumor Microenvironmentmentioning

confidence: 99%

Inflammasome Signaling: A Novel Paradigm of Hub Platform in Innate Immunity for Cancer Immunology and Immunotherapy

Liu

Shi

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Inflammasomes are fundamental innate immune mechanisms that promote inflammation and induce an inflammatory form of programmed cell death, pyroptosis. Pyroptotic inflammasome has been reported to be closely associated with tumorigenesis and prognosis of multiple cancers. Emerging studies show that the inflammasome assembly into a higher-order supramolecular complex has been utilized to evaluate the status of the innate immune response. The inflammasomes are now regarded as cellular signaling hubs of the innate immunity that drive the production of inflammatory cytokines and consequent recruitment of immune cells to the tumor sites. Herein, we provided an overview of molecular characteristics and biological properties of canonical and non-canonical inflammasome signaling in cancer immunology and immunotherapy. We also focus on the mechanism of regulating pyroptotic inflammasome in tumor cells, as well as the potential roles of inflammasome-mediated pyroptotic cell death in cancers, to explore the potential diagnostic and therapeutic markers contributing to the prevention and treatment of cancers.

show abstract

“…Since IL-1B causes immunosuppression 18 , inhibition of this cytokine in combination with immunotherapies has been found to promote anti-tumour immunity and impair primary tumour growth 19 . Therefore, administration of anti-IL-1 therapies in combination with immune-stimulatory drugs may provide effective therapeutic options for patients with breast cancer.…”

Section: Introductionmentioning

confidence: 99%

IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer

et al. 2021

View full text Add to dashboard Cite

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Using syngeneic IL-1B/IL1R1 knock out mouse models in combination with genetic manipulation of tumour cells to overexpress IL-1B/IL1R1, we found that IL-1B signalling elicited an opposite response in primary tumours compared with bone metastases. In primary tumours, IL-1B inhibited growth, by impairing the infiltration of innate immune cell subsets with potential anti-cancer functions but promoted enhanced tumour cell migration. In bone, IL-1B stimulated the development of osteolytic metastases. In syngeneic models of breast cancer, combining standard of care treatments (Doxorubicin and Zoledronic acid) with the IL-1 receptor antagonist Anakinra inhibited both primary tumour growth and metastasis. Anakinra had opposite effects on the immune response compared to standard of care treatment, and its anti-inflammatory signature was maintained in the combination therapy. These data suggest that targeting IL-1B signalling may provide a useful therapeutic approach to inhibit bone metastasis and improve efficacy of current treatments for breast cancer patients.

show abstract

IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D

Cited by 52 publications

References 60 publications

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy

Inflammasome Signaling: A Novel Paradigm of Hub Platform in Innate Immunity for Cancer Immunology and Immunotherapy

IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer

Contact Info

Product

Resources

About