Interleukin-1β and Cancer Rébé, Cédric; Ghiringhelli, François
Cancers,
07/2020, Volume:
12, Issue:
7
Journal Article
Peer reviewed
Open access
Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is ...required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Immunological aspects of cancer chemotherapy Kroemer, Guido; Apetoh, Lionel; Ghiringhelli, François ...
Nature reviews. Immunology,
200801, 2008-Jan, 2008-1-00, 20080101, Volume:
8, Issue:
1
Journal Article
Peer reviewed
Open access
Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer ...treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a ...key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the ...proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g. by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Resistance to chemo-immunotherapy is a major issue for the treatment of non-small cell lung cancer. In a recent paper we unravel the role of MAPK in the capacity of restraining the therapeutic ...efficacy of chemo-immunotherapy. Inhibition of the MAPK pathway using a MAP2K/MEK inhibitor in combination with chemotherapy could promote OPTN (optineurin)-dependent mitophagy of cancer cells. Mitochondria then degrade via autophagosomes and amphisomes and release mitochondrial DNA, which interacts with TLR9 located in these compartments. TLR9 activation promotes the production of the chemokine CXCL10 by cancer cells, which could further improve T cell recruitment and improve the efficacy of immunotherapy.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The accumulation of regulatory T cells (Tregs) at high density in various human carcinomas is generally associated with a poor prognosis, as expected from their capacity to inhibit antitumor ...immunity. Surprisingly, in patients bearing colorectal carcinoma (CRC), high regulatory T-cell infiltration is associated with a favorable prognosis, as shown by the analysis of seven clinical studies. To explain this paradox, we emphasize a putative role of the dense microbiological flora present in the large intestine with a trend toward translocation through the tumor. This microbiological hazard requires a T-cell-mediated inflammatory anti-microbial response that involves Th17 cells and can thereby promote cancer growth. This Th17-cell-dependent proinflammatory and tumor-enhancing response can be attenuated by Tregs, thus constituting a possible explanation for their favorable role in CRC prognosis. The link between a high density of FOXP3-positive cells in CRC immune infiltrates and favorable prognosis should lead us to consider tumor infiltrating Tregs as allies to be respected, rather than enemies to be destroyed during trials of CRC treatment.
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EMUNI, NUK, SBMB, SBNM, UL, UM, UPUK
Checkpoint blockade immunotherapy is a therapeutic revolution in cancer treatment. However, only 5% of patients with metastatic colorectal cancer benefit from these therapies, and these tumors ...genetically harbored microsatellite instability status. In contrast, tumors with stable microsatellites are considered resistant to immunotherapy, and standard treatment with chemotherapies is standard of care, with few chances of curative intent. In a recent clinical trial, we demonstrated that the combination of two chemotherapies with two immunotherapies promotes the recruitment and activation of the adaptive immune system at the tumor level, resulting in clinical benefit in a significant number of patients. In parallel, a biological study revealed biomarkers of response, including CTLA-4 expression and induction of a tumor-specific immune response.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Even though the discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, a high proportion of patients do not respond. Moreover, some types of cancers are ...refractory to these treatments. Thus, the need to find predictive biomarkers of efficacy and to evaluate the association with other treatments, such as chemotherapy or radiotherapy, appears to be essential. Because ICIs reactivate or maintain an active status of T cells, one possibility is to combine these treatments with therapies that engage an immune response against tumor cells. Thus, by inducing immunogenic cell death (ICD) of cancer cells, some conventional anticancer treatments induce such immune response and may have an interest to be combined with ICIs. In this review, we explore preclinical studies and clinical trials that evaluate the combination of ICIs with ICD inducers. More than inducing ICD, some of these treatments appear to modulate the tumor microenvironment and more particularly to inhibit immunosuppression, thus improving treatment efficacy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Modulation of the inflammatory response is one of the major issues of the 21st century due to its importance in the occurrence of various pathologies (cancer, autoimmune diseases, degenerative ...diseases) and their progression over time. Whether acute or chronic, the inflammatory response is directly related to the immune response through different subtypes of T lymphocytes. In addition, among the compounds capable of modulating the cells of the immune system, resveratrol, a polyphenol with pleiotropic biological properties, seems to be a good candidate. Indeed, resveratrol is able to alter the immune response by modulating the process of lymphocyte differentiation and subsequently diminishing the inflammatory-associated response. More specifically, thanks to its ability to act as a sirtuin-1 agonist, it can deacetylate the transcription factor STAT3 and alter nuclear factors essential to the process of lymphocyte differentiation. We present and discuss these different aspects in relation to various pathologies and how the alteration of the ratios between the different lymphocyte subtypes by resveratrol is an important element to take into account when studying its anti-inflammatory and immunomodulatory properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Immunotherapy using checkpoint inhibitor targeting PD-1 and PD-L1 revolutionized the treatment of microsatellite instable metastatic colon cancer. Such treatment is now a standard of care for these ...patients. However, when used as monotherapy checkpoint inhibitors targeting PD-1 and PD-L1 are not effective in metastatic colorectal cancer patients with microsatellite stable tumors. Recent advances in biology provide a rationale for this intrinsic resistance and support the evaluation of combination therapy to reverse resistance. This article will highlight recent findings on the mechanism of intrinsic resistance and recent advances in clinical trials for combination therapy.
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