Blunting age-associated chronic inflammation preserves hematopoiesis and immunity and reduces leukemogenesis

Henry, Curtis J.; Casás‐Selves, Matias; Kim, Jihye; Zaberezhnyy, Vadym; Aghili, Leila; Daniel, Ashley E.; Jimenez, Linda; Azam, Tania; McNamee, Eoin N.; Clambey, Eric T.; Klawitter, Jelena; Serkova, Natalie J.; Tan, Aik Choon; Dinarello, Charles A.; DeGregori, James

doi:10.4049/jimmunol.198.supp.60.8

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer cells alter their microenvironment, and recent data have substantiated the view that changes/evolution of the microenvironment is mechanistically linked to drug resistance (Hirata et al, 2015;Woolston et al, 2019). Furthermore, inflammation associated with changes during ageing promotes selection for cells with adaptive oncogenic phenotypes (Barcellos-Hoff et al, 2013;Henry et al, 2015;Laconi et al, 2020). In addition, a number of experiments have highlighted the ability of a healthy microenvironment to repress oncogenic transformation through various mechanisms such as immune surveillance and maintenance of tissue structure via the extracellular matrix and healthy tissue (stroma) surrounding the tumour (Strobl et al, 2020).…”

Section: Major Theme 3: Tumour and Microenvironmentmentioning

confidence: 98%

Identifying key questions in the ecology and evolution of cancer

Dujon

Aktipis

Alix‐Panabières

et al. 2021

Evolutionary Applications

View full text Add to dashboard Cite

The application of evolutionary and ecological principles to cancer prevention and treatment, as well as recognizing cancer as a selection force in nature, has gained impetus over the last 50 years. Following the initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear that using the eco-evolutionary framework is of key importance to understand cancer. We are now at a pivotal point where accumulating evidence starts to steer the future directions of the discipline and allows us to underpin the key challenges that remain to be addressed. Here, we aim to assess current advancements in the field and to suggest future directions for research.First, we summarize cancer research areas that, so far, have assimilated ecological and evolutionary principles into their approaches and illustrate their key importance. Then, we assembled 33 experts and identified 84 key questions, organized around nine major themes, to pave the foundations for research to come. We highlight the urgent need for broadening the portfolio of research directions to stimulate novel approaches at the interface of oncology and ecological and evolutionary sciences. We conclude that progressive and efficient cross-disciplinary collaborations that draw on the expertise of the fields of ecology, evolution and cancer are essential in order to efficiently address current and future questions about cancer. | INTRODUC TI ONThe application of evolutionary and ecological principles to preventing and treating cancer , as well as to understanding the impact of cancer on organismal health, fitness, species stability and ecosystem functioning (Thomas et al., 2017), has been gaining increasing attention and recognition among both oncologists and biologists since the seminal work of Cairns (1975), Nordling (1953 and Nowell (1976), more than 45 years ago. Most scientists today agree that this evolutionary view has deeply transformed the way we understand the biology of cancer-explaining its origin and the recrudescence of cancer cells as well as elucidating reasons for therapy failures. Following the theoretical development of a new interdisciplinary field that combines expertise from mathematicians, data scientists and biostatisticians, geneticists, evolutionary biologists, ecologists, physicists and oncologists, we are now at a pivotal point where empirical data and evidence are accumulating and guiding future directions of the discipline (Ujvari et al., 2017). We believe that the time has arrived to take stock of current advancements and to inform the course of future research. Cancer is a disease that impacts every country worldwide (18.1 million new cases and 9.6 million death in 2018; Bray et al., 2018), and these oncogenic processes are an inevitable phenomenon of metazoan life. Identifying the key questions in the ecology and evolution of cancer will provide a cornerstone in cancer and evolutionary research for the coming years. This will provide the basis for the development of efficient strategies to either preven...

show abstract

Section: Major Theme 3: Tumour and Microenvironmentmentioning

confidence: 98%

Identifying key questions in the ecology and evolution of cancer

Dujon

Aktipis

Alix‐Panabières

et al. 2021

Evolutionary Applications

View full text Add to dashboard Cite

show abstract

“…A decline of tissue maintenance systems in the elderly leads to alterations in the tissue environment inducing changes in selective pressures to direct evolution of mutant clones towards malignant phenotypes [57,91]. Illustrating the impact of environmental pressures on the course of evolutionary changes within an organism is the observation that hematopoietic stem cell mutants that fail to gain proliferative advantage in a young individual, may promote malignancy later in life due to aging-associated alterations in the cytokine milieu [92]. Thus, environmental factors such as the ecology of cell exchanges and organization of a tissue landscape contribute to cancer-protective functions, preventing cells from unlimited growth and invasive spread [93,94].…”

Section: Implications Of the Evolutionary Frameworkmentioning

confidence: 99%

Struggle within: evolution and ecology of somatic cell populations

Świątczak

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives.

show abstract

“…IL-37 reduces proinflammatory cytokine secretion in mouse macrophages, human monocytes, and epithelial cells upon stimulation with LPS or IL-1ß (30) and inhibits systemic inflammation in various murine disease models (30,(32)(33)(34)(35). IL-37 also displays an anti-inflammatory role within the epithelium, as shown in experiments on T84 colonic carcinoma cells (36), human and murine intestinal organoids (37), and dextran sodium sulfate (DSS)-colitis mice (32).…”

Section: Introductionmentioning

confidence: 99%

Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity

Kröhn,

Azabdaftari,

Heuberger

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Background and AimsIntestinal epithelial cells separate the luminal flora from lamina propria immune cells and regulate innate immune responses in the gut. An imbalance of the mucosal immune response and disrupted intestinal barrier integrity contribute to the evolution of inflammatory bowel diseases. Interleukin (IL)-37 has broad anti- inflammatory activity and is expressed by the human intestinal epithelium. Mice ectopically expressing human IL-37 show reduced epithelial damage and inflammation after DSS-induced colitis. Here, we investigated the impact of IL-37 on the innate immune response and tight junction protein expression of mouse intestinal organoids and the modulation of IL37 expression in human intestinal organoids.MethodsMurine intestinal organoids were generated from IL-37tg and wildtype mice. Human ileal organoids were generated from healthy young donors.ResultsExpression of transgene IL-37 or recombinant IL-37 protein did not significantly reduce overall proinflammatory cytokine mRNA expression in murine intestinal organoids. However, higher IL37 expression correlated with a reduced proinflammatory cytokine response in murine colonic organoids. IL37 mRNA expression in human ileal organoids was modulated by proinflammatory cytokines showing an increased expression upon TNF-α-stimulation and decreased expression upon IFN-gamma stimulation. Transgene IL-37 expression did not rescue TNF-α-induced changes in morphology as well as ZO-1, occludin, claudin-2, and E-cadherin expression patterns of murine jejunal organoids.ConclusionsWe speculate that the anti-inflammatory activity of IL-37 in the intestine is mainly mediated by lamina propria immune cells protecting intestinal epithelial integrity.

show abstract

Blunting age-associated chronic inflammation preserves hematopoiesis and immunity and reduces leukemogenesis

Cited by 3 publications

References 0 publications

Identifying key questions in the ecology and evolution of cancer

Identifying key questions in the ecology and evolution of cancer

Struggle within: evolution and ecology of somatic cell populations

Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity

Contact Info

Product

Resources

About