Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well ...understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses. Antibiotic-mediated depletion or gnotobiotic exclusion of fungi enhances responsiveness to radiation, whereas antibiotic-mediated depletion of bacteria reduces responsiveness and is associated with overgrowth of commensal fungi. Further, elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in patients with breast cancer and is required for the effects of commensal fungi in mouse models of radiation therapy.
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•Commensal bacteria support antitumor T cell responses following radiation therapy•Depletion of intestinal bacteria leads to expansion of commensal fungal populations•Commensal fungi promote pro-tumor macrophage actions by impeding antitumor T cells•Tumor-associated macrophages sense fungi through a Dectin-1-mediated mechanism
Depletion of commensal bacteria leads to expansion of commensal fungi and reduced antitumor immunity following irradiation of tumors. Targeting commensal fungi enhanced the radiation-induced antitumor immune response by reducing macrophage-mediated immunosuppression. Thus, Shiao et al. demonstrate opposing effects of commensal bacteria and fungi on antitumor immunity following radiation.
Radiation continues to play a major role in the treatment of almost every cancer type. Traditional radiation studies focused on its ability to damage DNA, but recent evidence has demonstrated that a ...key mechanism driving the efficacy of radiation
is the immune response triggered in irradiated tissue. Innate immune cells including macrophages, dendritic cells, and natural killer cells are key mediators of the radiation-induced immune response. They regulate the sensing of radiation-mediated damage and subsequent radiation-induced inflammation. Given the importance of innate immune cells as determinants of the post-radiation anti-tumor immune response, much research has been devoted to identify ways to both enhance the innate immune response and prevent their ability to suppress ongoing immune responses. In this review, we will discuss how the innate immune system shapes anti-tumor immunity following radiation and highlight key strategies directed at the innate immune response to enhance the efficacy of radiation.
Abstract
Every year over 200,000 North American women are diagnosed with breast cancer, which is the second leading cause of cancer death among women. The introduction of effective immunotherapies ...has revolutionized patient care in many cancers, including breast, but only a subset of patients exhibit clinical response. Factors determining a patient’s response to immunotherapy is an area of intense research. The microbiome is one potential contributing factor. The human intestinal microbiome is comprised largely of bacteria, but also harbors fungi, viruses and archaea that undoubtedly have significant biological functions. Recent reports have detailed the association of specific strains of bacteria with positive response to PD-1/PDL1 therapy in several cancers however, little is known regarding the involvement of commensal fungi. Previous work in our lab found a high diversity of fungi associated with the human gut, which interact with the immune system and influence the severity of gastrointestinal inflammation and allergic airway disease. Using a syngeneic murine model of triple negative breast cancer, we found that antifungal treatment sensitizes previously resistant tumors to anti-PD1 therapy, leading to a significant decrease in growth rate as well as increased survival compared to anti-PD-1 treatment alone. Antifungal treatment altered the microbiome composition as evidenced by 16s and ITS1 sequencing of fecal pellets, as well as altered the tumor immune compartment to promote anti-tumor activity when combined with anti-PD1. These data suggest fungi have a role in shaping the immune-tumor microenvironment and provide insight into how perturbation of the microbiome might improve response to immunotherapy.
Achieving choice is proposed as a quality marker. But little is known about what influences preferences especially among older adults. We aimed to determine and compare, across three countries, ...factors associated with preferences for place of death and treatment, and actual site of death.
We recruited adults aged ≥65-years from hospital-based multiprofessional palliative care services in London, Dublin, New York, and followed them for >17 months. All services offered consultation on hospital wards, support for existing clinical teams, outpatient services and received funding from their National Health Service and/or relevant Insurance reimbursements. The New York service additionally had 10 inpatient beds. All worked with and referred patients to local hospices. Face-to-face interviews recorded most and least preferred place of death, treatment goal priorities, demographic and clinical information using validated questionnaires. Multivariable and multilevel analyses assessed associated factors.
One hundred and thirty eight older adults (64 London, 59 Dublin, 15 New York) were recruited, 110 died during follow-up. Home was the most preferred place of death (77/138, 56%) followed by inpatient palliative care/hospice units (22%). Hospital was least preferred (35/138, 25%), followed by nursing home (20%) and home (16%); hospice/palliative care unit was rarely least preferred (4%). Most respondents prioritised improving quality of life, either alone (54%), or equal with life extension (39%); few (3%) chose only life extension. There were no significant differences between countries. Main associates with home preference were: cancer diagnosis (OR 3.72, 95% CI 1.40-9.90) and living with someone (OR 2.19, 1.33-3.62). Adults with non-cancer diagnoses were more likely to prefer palliative care units (OR 2.39, 1.14-5.03). Conversely, functional independence (OR 1.05, 1.04-1.06) and valuing quality of life (OR 3.11, 2.89-3.36) were associated with dying at home. There was a mismatch between preferences and achievements - of 85 people who preferred home or a palliative care unit, 19 (25%) achieved their first preference.
Although home is the most common first preference, it is polarising and for 16% it is the least preferred. Inpatient palliative care unit emerges as the second most preferred place, is rarely least preferred, and yet was often not achieved for those who wanted to die there. Factors affecting stated preferences and met preferences differ. Available services, notably community support and palliative care units, require expansion. Contrasting actual place of death with capacity for meeting patient and family needs may be a better quality indicator than simply 'achieved preferences'.
All plants studied in natural ecosystemsare symbiotic with fungi that either resideentirely (endophytes) or partially(mycorrhizae) within plants. Thesesymbioses appear to adapt to biotic andabiotic ...stresses and may be responsible forthe survival of both plant hosts and fungalsymbionts in high stress habitats. Here wedescribe the role of symbiotic fungi inplant stress tolerance and present astrategy based on adaptive symbiosis topotentially mitigate the impacts of globalchange on plant communities.PUBLICATION ABSTRACT
Our healthcare institution was one of the first to see SARS CoV-2 cases in the country. We describe the early COVID-19 experience of a private hospital in the Philippines and discuss the healthcare ...system response in the setting of surge capacity.
We reviewed the medical records of adult COVID-19 hospitalized patients admitted in March 2020. We reported their demographic and clinical characteristics using descriptive statistics.
Of 40 patients admitted, 23 (57.5%) were male and 19 (47.5%) were aged <60 years. Most (n = 27, 67.5%) had moderate-risk, 9 (22.5%) had high-risk, and 4 (10%) had low-risk COVID-19. SARS-CoV-2 testing took 5.5 (range 1–10) days. Overall mortality rate was 6/40 (15.0%). Clinical cure was documented in all low-risk patients, 25 (92.6%) moderate-risk patients, and only 1 (11.1%) high-risk patient. In response to the surge, the hospital rapidly introduced one-way traffic systems, dedicated screening, triage and Emergency Department areas for COVID-19, a clinical pathway, engineering controls, patient cohorting, and strict infection prevention and control measures.
Majority of patients recovered from COVID-19. Older age and high-risk pneumonia were associated with poor outcomes. Adaptations to hospital structure and staff were quickly made in response to surge capacity, although our response was hampered by prolonged time to COVID-19 confirmation. Our study underscores the urgent need for rapid adaptive response by the healthcare system to address the surge of cases.
Thermotolerance Generated by Plant/Fungal Symbiosis Redman, Regina S.; Sheehan, Kathy B.; Stout, Richard G. ...
Science (American Association for the Advancement of Science),
2002-Nov-22, Letnik:
298, Številka:
5598
Journal Article
Recenzirano
Plants inhabiting natural ecosystems are known to have established a symbiotic relationship with fungi. These fungi may exert a significant influence on plant adaptation to selective pressures. A ...study was implemented to evaluate whether mutualistic fungi contributed meaningfully to plant adaption. As part of the effort, researchers collected 200 samples of Dichanthelium lanuginosum plants from geothermal soils at 10 locations in Lassen Volcanic National Park and Yellowstone National Park. Soils at these sites experience significant annual fluctuations in temperature, ranging from 20-50 degree C. Both plant and root samples were evaluated for fungal colonization. Evidence of thermotolerance in the plants resulting from their symbiotic relationship with fungi is examined.
Thermotolerance generated by plant/fungal synbiosis Redman, Regina S; Sheehan, Kathy B; Stout, Richard G ...
Science (American Association for the Advancement of Science),
11/2002, Letnik:
298, Številka:
5598
Journal Article
Recenzirano
To test whether mutualistic fungi contribute to plant adaptation, Redman et al collected 200 Dichanthelium lanuginosum plants from geothermal soils at 10 sites in Lassen Volcanic (LVNP) and ...Yellowstone (YNP) National Parks. The beneficial effect of fungal symbiosis increased with soil temperatures.
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