The secretion of interferon gamma (IFNG, best known as IFNγ) by immune effector cells generally mediates potent anticancer effects. Recent data from Beziaud et al. demonstrate that—at least in some ...circumstances—IFNγ can edit the breast cancer microenvironment to promote stemness, disease progression and resistance to (immuno)therapy.
Cancer cell dormancy is a common feature of human tumors and represents a major clinical barrier to the long-term efficacy of anticancer therapies. Dormant cancer cells, either in primary tumors or ...disseminated in secondary organs, may reawaken and relapse into a more aggressive disease. The mechanisms underpinning dormancy entry and exit strongly resemble those governing cancer cell stemness and include intrinsic and contextual cues. Cellular and molecular components of the tumor microenvironment persistently interact with cancer cells. This dialog is highly dynamic, as it evolves over time and space, strongly cooperates with intrinsic cell nets, and governs cancer cell features (like quiescence and stemness) and fate (survival and outgrowth). Therefore, there is a need for deeper insight into the biology of dormant cancer (stem) cells and the mechanisms regulating the equilibrium quiescence-
-proliferation are vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. Here, we review and discuss microenvironmental regulations of cancer dormancy and its parallels with cancer stemness, and offer insights into the therapeutic strategies adopted to prevent a lethal recurrence, by either eradicating resident dormant cancer (stem) cells or maintaining them in a dormant state.
Type I Interferons (IFNs) are key regulators of natural and therapy-induced host defense against viral infection and cancer. Several years of remarkable progress in the field of oncoimmunology have ...revealed the dual nature of these cytokines. Hence, Type I IFNs may trigger anti-tumoral responses, while leading immune dysfunction and disease progression. This dichotomy relies on the duration and intensity of the transduced signaling, the nature of the unleashed IFN stimulated genes, and the subset of responding cells. Here, we discuss the role of Type I IFNs in the evolving relationship between the host immune system and cancer, as we offer a view of the therapeutic strategies that exploit and require an intact Type I IFN signaling, and the role of these cytokines in inducing adaptive resistance. A deep understanding of the complex, yet highly regulated, network of Type I IFN triggered molecular pathways will help find a timely and immune“logical” way to exploit these cytokines for anticancer therapy.
Cancer stem cells (CSCs) are broadly considered immature, multipotent, tumorigenic cells within the tumor mass, endowed with the ability to self-renew and escape immune control. All these features ...contribute to place CSCs at the pinnacle of tumor aggressiveness and (immune) therapy resistance. The immune privileged status of CSCs is induced and preserved by various mechanisms that directly affect them (e.g., the downregulation of the major histocompatibility complex class I) and indirectly are induced in the host immune cells (e.g., activation of immune suppressive cells). Therefore, deeper insights into the immuno-biology of CSCs are essential in our pursuit to find new therapeutic opportunities that eradicate cancer (stem) cells. Here, we review and discuss the ability of CSCs to evade the innate and adaptive immune system, as we offer a view of the immunotherapeutic strategies adopted to potentiate and address specific subsets of (engineered) immune cells against CSCs.
Patients who leave Emergency Department before physician's visit (LWBS) or during treatment (LDT) represent a useful indicator of the emergency care's quality. The profile of patients LWBS was ...described: they are generally males, young, with lower urgency triage allocation and longer waiting time. They have a greater risk of ED re-admission compared to discharged patients, but effect on hospitalization and mortality are more controversial. The aims of this study are to identify determinants and adverse short term outcomes for LWBS and LDT patients.
This is a retrospective cohort study that include all ED visits of LWBS, LDT and discharged patients in 2015 in the Lazio region, Central Italy. Determinants of LWBS or LDT were selected from gender, age, citizenship, residence area, triage category, chronic comorbidities, number of uncompleted ED visit in the previous year, mode of arrival in ED, time-band, day of the week, waiting time and ED crowding, using a multi-level logistic regression. A multivariate logistic regression was used to test if LWBS or LDT have a greater risk of short term adverse outcome compared to discharged patients.
The cohort consists in 835,440 visits in ED, 86.8% subjects visited and discharged, 8.9% subjects are LWBS patients and 4.3% LDT. LWBS and LDT patients are mainly young, males, with a less severe triage, with long waiting times in ED. Moreover, ED crowding and leaving ED before physician's visit in the previous year are risk factors of self-discharging. LWBS and LDT patients have a higher risk of readmission (LWBS: OR = 4.63, 95%CI 4.5-4.7; OR = 2.89, 95%CI 2.8-2.9; LDT: OR = 3.12, 95%CI 3-3.2; OR = 2.25, 95%CI2.2-2.3 for readmissions within 2 and 7 days respectively) and hospitalization (LWBS: OR = 3.65, 95%CI 3.4-3.9; OR = 2.25, 95%CI 2.1-2.4; LDT: OR = 3.96, 95%CI 3.6-4.3; OR = 2.62, 95%CI 2.4-2.8 for hospitalization within 2 and 7 days respectively). Furthermore, we find a mortality excess of risk for LWBS patients compared to the reference group (OR = 2.56, 95%CI1.6-4.2; OR = 1.7, 95%CI 1.3-2.2 within 2 and 7 days respectively).
Determinants of LWBS confirmed what already known, but LDT patients should be further investigated. There could be adverse health effects for people with LWBS and LDT behaviour. This could be an issue that the Regional Health System should deal with.
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of pathologically activated, mostly immature, myeloid cells that exert robust immunosuppressive functions. MDSCs expand during ...oncogenesis and have been linked to accelerated disease progression and resistance to treatment in both preclinical tumor models and patients with cancer. Thus, MDSCs stand out as promising targets for the development of novel immunotherapeutic regimens with superior efficacy. Here, we summarize accumulating preclinical and clinical evidence indicating that MDSCs also hamper the efficacy of radiotherapy (RT), as we critically discuss the potential of MDSC-targeting strategies as tools to achieve superior immunotherapeutic tumor control by RT in the clinic.
Newly formed malignant cells must escape immunosurveillance to generate progressing neoplastic lesions of clinical relevance. Recent data indicate that the immunogenicity of nascent cancer cells, at ...least in some settings, is dictated by inherent epigenetic mechanisms rather than by immunoediting and the consequent Darwinian selection of poorly immunogenic phenotypes.
Recent work supports that the immunogenicity of cancer cells is regulated by cell‐intrinsic epigenetic mechanisms involving the RNA‐binding protein CSDE1.
OBJECTIVES
Although thymoma is considered a relatively indolent neoplasia, patients affected by this disease are at high risk of developing second tumours (STs). The aim of this study is to assess ...the risk of developing STs after surgical thymoma resection.
METHODS
A multicentre retrospective study of patients operated on for thymoma within five Italian Thoracic Surgery Institutions, between 2000 and 2011, was conducted. The overall STs number and incidence were calculated. The number of metachronous STs was compared with the expected cancer number (ECN) in an Italian population, and the standardized incidence ratio (SIR) and 95% confidence intervals were calculated. Potential variables of STs predictors were also evaluated.
RESULTS
There were 302 patients; myasthenia gravis (MG) was observed in 166 (55%) and other autoimmune syndromes in 49 of them. In 118 patients (39.1%), the Masaoka thymoma stage was greater than II and in 194, the WHO histological type ranged from B1 to C. Fifty STs were observed (28 metachronous, 4 synchronous and 18 detected before thymoma). The observed metachronous STs number was significantly higher than ECN. An increased risk of STs development was observed in advanced stage thymomas and in those with histological high grade. On the contrary, MG seems to be a protective factor in STs development.
CONCLUSIONS
Our study confirms the high risk of developing STs in patients with thymoma. Aggressive forms of thymoma are those in which this risk appears to be more evident. The central role of an intrinsic immune system alteration might be the key to interpret this phenomenon.
Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.
...We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.
The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 1.07-1.47 to 1.10 0.94-1.30 in the first, and from 1.26 1.08-1.47 to 1.10 0.93-1.29 in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children.
The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.
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