Explore the vast range of titles available.

Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.

Ultraviolet-radiation suppresses cell-mediated immunity in healthy humans. It has been postulated that, in the short term, this immunosuppression prevents autoimmune responses to ultraviolet-radiation damaged skin. Patients with polymorphic light eruption (PLE) demonstrate abnormal responses to ultraviolet-radiation suggestive of an immune response to an ultraviolet-radiation-induced antigen. We investigated whether PLE patients (n=22) were resistant to ultraviolet-radiation-induced immunosuppression compared to skin-type, aged-matched controls (n=23). Groups of patients and controls (six subjects per group) received a single dose of solar-simulated ultraviolet-radiation of either 0, 0.6, 1 or 2 minimal erythema doses (MED). Erythema was quantified using a reflectance meter and all volunteers were sensitised on the irradiated site with dinitrochlorobenzene. Contact hypersensitivity responses (CHS) to dinitrochlorobenzene were quantified after challenge using ultrasound. Ultraviolet-radiation-induced erythema was comparable in patients and controls. CHS was comparable in unirradiated patients and controls. UVR-induced a dose-dependent suppression of CHS in all volunteers but patients were more resistant to immunosuppression after 1MED. Exposure to 1MED suppressed CHS by 78% in controls but induced less suppression in patients (44%, p < 0.01). Our data suggest that PLE patients have a flaw in their immunoregulatory response to ultraviolet-radiation it is only apparent over a narrow dose range around 1 MED.

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

It is hypothesized that polymorphic light eruption is characterized by a partial failure of ultraviolet radiation-induced immunosuppression, resulting in a delayed-type hypersensitivity response to photo-induced antigens. We aimed to study the susceptibility of PLE patients to UVR-induced immunosuppression, by measuring the strength of sensitization to 2,4-dinitrochlorobenzene after UVR exposure, and to diphenylcyclopropenone without UVR exposure, in subjects with PLE and controls. Thirteen PLE patients and 11 controls were exposed to 1 minimum erythema dose (MED) of UVR delivered from Waldmann UV-6 bulbs to the upper inner arm. Twenty-four hours later at the same site they were exposed to a sensitizing dose of 2,4-dinitrochlorobenzene. One week later they were exposed to a sensitizing dose of diphenylcyclopropenone at a nonirradiated site. Three weeks later all subjects were challenged with four doses of 2,4-dinitrochlorobenzene and four doses of diphenylcyclopropenone. The resulting increase in skin thickness was measured with Harpenden callipers and summed over the four doses, to give a single value representing the reactivity of the subject to 2,4-dinitrochlorobenzene (ΣDN) and diphenylcyclopropenone (ΣDP). Among all subjects, there was a very strong correlation between ΣDN and ΣDP (Pearson correlation 0.56, p=0.004). The strength of the reaction to 2,4-dinitrochlorobenzene relative to the reaction to diphenylcyclopropenone was significantly greater among PLE patients than controls (p=0.04 independent samples t test of ΣDP–ΣDN). We conclude that induction of sensitization by 2,4-dinitrochlorobenzene is suppressed less by UVR in patients with PLE than in healthy controls.

Abstract Radiotherapy is cytotoxic to tumor cells and is therefore a critical component of therapy for many malignancies, including glioblastoma (GBM). We now appreciate the value of the immunomodulatory effects of radiation that may be important to overall therapeutic success in some patients with this primary brain tumor. Although potentially beneficial immune-stimulating properties of radiotherapy treatment have been the focus of recent study, this modality is actually at the same time associated with the depletion of lymphocytes, which are crucial to the defense against neoplastic development and progression. In this review, we describe the association of systemic lymphopenia with poor tumor outcome, present evidence that radiotherapy is an important contributing cause of lymphodepletion, describe the systemic immune context of tumor and brain injury that contributes to immunosuppression, describe other contributing factors to lymphopenia including concomitant medications and treatments, and speculate about the role of the normal physiologic response to brain injury in the immunosuppressive dynamics of GBM. Radiotherapy is one significant and potentially actionable iatrogenic suppressor of immune response that may be limiting the success of therapy in GBM and other tumor types. Altered strategies for radiotherapy more permissive of a vigorous antineoplastic immune response may improve outcome for malignancy.

The effects of acute exposure to low- and high-dose radiation on the quantitative and functional parameters of the immune system were analyzed. C57BL/6 mice were irradiated with different doses of γ radiation (0.01, 0.05, 0.1, 0.5 and 2 Gy) and splenocytes were isolated at various times. Alterations in the distribution and surviving fraction of splenocyte subsets such as CD4+ and CD8+ T lymphocytes, regulatory T cells (Treg), natural killer (NK) cells, dendritic cells (DCs) and B lymphocytes were analyzed by flow cytometry. Apoptosis frequency was quantified by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method 4 h after irradiation. Cytokine expression was investigated by real-time reverse transcription-polymerase chain reaction (RT-PCR). Low doses decreased apoptosis in the splenocyte subpopulations studied most prominently in NK cells and DCs. Exposure to 2 Gy increased apoptosis in all splenocyte subpopulations; B cells were the most sensitive and NK cells and DCs the least sensitive. The lowest cell numbers were measured 3 days after irradiation, with minor changes by day 7. CD8+ and B cells were rather resistant to low doses but were very sensitive to 2 Gy, while NK cells, DCs and Treg cells were much more resistant to high doses. Expression of the T-helper 1 (Th1)- and helper 2 (Th2)-type cytokines decreased after low doses and increased after high doses. Interleukin 6 (IL-6) reacted at early times and IL-10 at later times. IL-5 levels were consistently elevated. These data highlight the differences in the responses of different splenocyte subpopulations to low- and high-dose radiation.

Key Points Distant metastasis remains a frequent cause of death, even after locoregional disease control is achieved using surgery, radiotherapy, and/or systemic therapy Antitumour therapies can, under some circumstances, mobilize tumour cells into the peripheral circulation that might influence the risk of distant metastasis Irradiation can enable tumour cells to acquire properties that facilitate their dissemination and the subsequent generation of metastases Several mechanisms might explain a metastasis-promoting effect derived from surgical procedures, such as tissue disruption and leakage of blood containing tumour cells A potential link between systemic therapies and metastasis has not been established, but the results of isolated studies indicate that this question needs to be addressed The risk of distant failure from antitumour therapy can potentially be reduced if treatment-related factors capable of promoting metastasis are identified, and targeted therapeutically Distant metastasis remains a common cause of death in patients with solid tumours, even after treatment with surgery, radiotherapy and/or chemotherapy. Treatment itself can sometimes cause or promote metastasis by increasing the number of circulating tumour cells. The authors of this article discuss preclinical and clinical data concerning cancer treatments, circulating tumour cell mobilization and other factors that might promote metastasis. Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common — and usually fatal — mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers; however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival.

The acute response of human skin to UVB radiation has not been fully characterized. We sought to define the cutaneous response at 24hours following narrowband UVB (NB-UVB, 312-nm peak), a therapeutically relevant source of UVB, using transcriptional profiling, immunohistochemistry, and immunofluorescence. There were 1,522 unique differentially regulated genes, including upregulated genes encoding antimicrobial peptides (AMPs) (S100A7, S100A12, human beta-defensin 2, and elafin), as well as neutrophil and monocyte/dendritic cell (DC) chemoattractants (IL-8, CXCL1, CCL20, CCL2). Ingenuity pathway analysis demonstrated activation of innate defense and early adaptive immune pathways. Immunohistochemistry confirmed increased epidermal staining for AMPs (S100A7, S100A12, human beta-defensin 2, and elafin). Inflammatory myeloid CD11c+BDCA1− DCs were increased in irradiated skin, which were immature as shown by minimal colocalization with DC-LAMP, and coexpressed inflammatory markers tumor necrosis factor (TNF) and TNF–related apoptosis-inducing ligand in irradiated skin. There were increased BDCA3+ DCs, a cross-presenting DC subtype with immunosuppressive functions, and these cells have not been previously characterized as part of the response to UVB. These results show that the acute response of human skin to erythemogenic doses of NB-UVB includes activation of innate defense mechanisms, as well as early infiltration of multiple subtypes of inflammatory DCs, which could serve as a link between innate and adaptive immunity.

It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8 + T cells, but decreased the frequency of inhibitory Tregs. Intracellular staining showed that after HSRT, peripheral CD8 + T cells were transformed into activated T cells, which express high levels of TNF-α, IFN-γ, granzyme B and IL-2. HSRT also increased the production of IL-2, TNF-α, and IFN-γ but down-regulated the production of TGF-β in CD4 + T cells. The frequencies of naïve B cells and double-negative B cells were lower, while the proportions of MZ-like B cells, transitional B cells and plasmablast cells were higher after HSRT. Collectively, our results demonstrate that HSRT activates the peripheral immune response and indicate the dynamic variation in peripheral lymphocytes after HSRT, which is very important for optimizing combination treatments in clinical practice.

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.