15. Iron and Its Role in Cancer Defense: A Double-Edged Sword

Thévenod, Frank

doi:10.1515/9783110470734-021

Cited by 25 publications

(25 citation statements)

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“…Indeed, iron may contribute to tumor initiation, and it is also a fundamental nutrient that favors cancer cell proliferation. Iron is thus also essential for maintaining the rapid growth rate of cancer cells that require iron-dependent enzymes for DNA synthesis 17 . Moreover, iron plays a pivotal role in the function of OXPHOS and the tricarboxylic acid cycle.…”

Section: Discussionmentioning

confidence: 99%

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

124

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The identification of prognostic and predictive markers is crucial for choosing the most appropriate management method for ovarian cancer patients. We aimed to assess the prognostic role of tumorassociated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage highgrade serous ovarian cancer as well as patients with other histotypes of ovarian cancer and patients with ovarian metastasis from other sites between June 2013 and December 2018. Patients were enrolled at the time of laparoscopic surgery before receiving any antineoplastic treatment. We found that patients with high-grade serous papillary ovarian cancers had a prevalence of M1 TAMs, a higher M1/M2 ratio, and a longer overall survival (OS) and progression-free survival (PFS) than other patients. Regression analysis confirmed that there was a significant positive association between the M1/M2 ratio and an improved OS, PFS and platinum-free interval (PFI), both in the entire population and in patients stratified according to tumor type and initial surgery. Kaplan-Meier analysis was performed after the patients were divided into 2 groups according to the median M1/M2 ratio and revealed that patients with a high M1/M2 ratio had a higher OS, PFS and PFI than those with a low M1/M2 ratio. In conclusion, the prognostic and predictive role of TAM polarization in the tumor microenvironment could be of great clinical relevance and may allow the early identification of patients who are likely to respond to therapy. Further studies in a larger prospective sample are warranted.www.nature.com/scientificreports www.nature.com/scientificreports/ linear relationship (β coefficient = 0.504, 95% CI 0.493-10.334, p = 0.033) was found between the platinum-free interval and M1/M2 ratio (Fig. 2).The median value for the M1/M2 ratio was 1.4. Then, we analyzed the difference in OS and PFS by Kaplan-Meier curve analysis and log-rank analysis between patients with an M1/M2 ratio ≥ 1.4 and those with an M1/M2 ratio < 1.4. We found that patients with an M1/M2 ratio ≥ 1.4 had a significantly longer OS (34 months versus 18 months, HR 2.7483, 95% CI: 1.1667-6.4736; p = 0.0207), PFS (24 months versus 9 months, HR 2.1285, 95% CI: 1.0461-4.3309; p = 0.0371) and PFI (12 months versus 6 months, HR 3.3959, 95% CI 1.2471-9.2469; p = 0.0168) ( Fig. 3). Scientific RepoRtS |(2020) 10:6096 | https://doi.

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Section: Discussionmentioning

confidence: 99%

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

124

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“…In order to control iron availability, immune cells adapt their phenotype accordingly to defend the host against invading pathogens. Since tumor cells might be recognized as foreign in the first place, it is not surprising that immune cells get polarized to adjust the iron metabolism at the systemic as well as local tumor levels [51,52,53]. As a consequence, tumor cells compete for iron with immune cells of their local microenvironment.…”

Section: Iron In the Tumor Microenvironment—role Of Tumor-associatmentioning

confidence: 99%

Iron as a Central Player and Promising Target in Cancer Progression

Jung

Mertens

Tomat

et al. 2019

IJMS

216

192

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Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.

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“…Cancer biology and immune surveillance are inseparably interconnected ( 17 ). A central nexus of this linkage is the competition for iron between neoplastic cells and the immune system which takes place both at the systemic level and in the microenvironment ( 18 ). Presumably, immune-driven adaptations of iron homeostasis in the presence of inflammatory stimuli have evolved during evolution as mechanisms to fight off bacteria and other pathogens, most of which require iron as essential growth factor ( 19 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

Iron in the Tumor Microenvironment—Connecting the Dots

et al. 2018

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Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic immune activation in the setting of malignancy alters systemic iron homeostasis and directs iron fluxes into myeloid cells. While this response aims at withdrawing iron from tumor cells, it may impair the effector functions of tumor-associated macrophages and will result in iron-restricted erythropoiesis and the development of anemia, subsequently. This review summarizes our current knowledge of the interconnections of iron homeostasis with cancer biology, discusses current clinical controversies in the treatment of anemia of cancer and focuses on the potential roles of iron in the solid tumor microenvironment, also speculating on yet unknown molecular mechanisms.

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15. Iron and Its Role in Cancer Defense: A Double-Edged Sword

Cited by 25 publications

References 0 publications

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Iron as a Central Player and Promising Target in Cancer Progression

Iron in the Tumor Microenvironment—Connecting the Dots

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