Irradiation or radiotherapy and immune

PURPOSES: Lymphopenia is extensively studied, but not circulating leucocyte subpopulations, which however have distinct roles in tumor tolerance. Proton therapy has been shown to have a lesser impact on the immune system than conventional X-ray radiotherapy through lower dose exposure to healthy tissues. We explored the differential effects of brain X-ray and proton irradiation on circulating leucocyte subpopulations. MATERIALS AND METHODS: Leucocyte subpopulation counts from tumor-free mice were obtained 12 hours after 4 fractions of 2...

Glioblastoma (GBM), a WHO grade IV glioma, is a malignant primary brain tumour for which combination of surgery, chemotherapy and radiotherapy is the first-line approach despite adverse effects. Tumour microenvironment (TME) is characterized by an interplay of cells and soluble factors holding a critical role in neoplastic development. Significant pathophysiological changes have been found in GBM TME, such as glia activation and oxidative stress. Microglia play a crucial role in favouring GBM growth, representing target cells of immune escape mechanisms...

BACKGROUND AND PURPOSE: Although proton therapy is increasingly being used in the treatment of paediatric and adult brain tumours, there are still uncertainties surrounding the biological effect of protons on the normal brain. Microglia, the brain-resident macrophages, have been shown to play a role in the development of radiation-induced neurotoxicity. However, their molecular and hence functional response to proton irradiation remains unknown. This study investigates the effect of protons on microglia by comparing the effect of photons and protons as well as the influence of age and different irradiated volumes...

Radiotherapy of the whole body is called total body irradiation (TBI). It is a well-established component of conditioning regimens before stem cell transplantation in juvenile leukemia. The patient was a three-year-old child with a diagnosis of B-cell acute lymphoblastic leukemia and planned for stem cell transplantation. He was given TBI under anesthesia for three consecutive days prior to the bone marrow transplantation under general anesthesia. The important concerns were related to neutropenia/immune suppression, parental consent for repeated anesthesia, nothing per oral guidelines for the TBI treatment, the possibility of high-grade fever, high chance of respiratory tract infections with repeated anesthesia exposure, etc...

PURPOSE: Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy...

It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof. This work seeks to address these discrepancies, and uses the lessons learned from both positive and negative trials, including the most cutting-edge data available, in order to guide future clinical trial design and clarify the ideal/expected role of combinatorial therapy going forward...

Neutrophils are known to contribute in many aspects of tumor progression and metastasis. The presence of neutrophils or neutrophil-derived mediators in the tumor microenvironment has been associated with poor prognosis in several types of solid tumors. However, the effects of classical cancer treatments such as radiation therapy on neutrophils are poorly understood. Furthermore, the cellular composition and distribution of immune cells in the tumor is of increasing interest in cancer research and new imaging technologies allow to perform more complex spatial analyses within tumor tissues...

PURPOSE: Radiotherapy (RT) is a widely employed anti-cancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. This study is to investigate immune suppressive factors of radiotherapy. EXPERIMENTAL DESIGN: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. RESULTS: Through analysis of PD-L1 expression and MDSC frequencies using patient PBMC and murine two-tumor and metastasis model, we report that local irradiation can induce a systemic increase in MDSCs, as well as PD-L1 expression on DCs and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, non-irradiated tissue...

BACKGROUND: Breast cancer (BC) is the most common form of cancer among women and the second leading cause of cancer-related death worldwide. Several malignancies can be successfully treated with radiation (RT), although radioresistance is still a major contributor to radiotherapy failure. Ionizing radiation (IR) induces pyroptosis in cancer cells. Pyroptosis is a designed method of death connected to routine immunity and directly related to the body ROS content. Objective for the study: The aim of this work was to investigate the role of serum GSDMD-CT, nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) and IL-18 as predictors of pyroptotic cell death mechanism induced by radiotherapy in breast cancer patients...

INTRODUCTION: The role of the immune system in the efficacy of radiotherapy (RT) has been well established. We examined the role of neoplasia-related and treatment-induced lymphopenia in the outcome of RT or chemoradiotherapy (CRT) in squamous cell laryngeal cancer. MATERIALS AND METHODS: We retrospectively analyzed a series of 135 laryngeal carcinomas treated with radical or postoperative RT/CRT. Six lymphocyte-related variables were defined and examined: i. lymphocyte counts (LCs) before a brief course of induction chemotherapy, ii...

BACKGROUND AND PURPOSE: As an advanced radiotherapy technique, carbon ion radiotherapy has demonstrated good efficacy and low toxicity for prostate cancer patients, but the radiobiological mechanism of killing tumor cells has not been fully elucidated. This study aims to explore the antitumor effects of carbon ion irradiation (CIR) through investigating the immune response induced by CIR in prostate cancer-bearing mice and the underlying molecular mechanism. MATERIALS AND METHODS: We established subcutaneous transplantation tumor models of prostate cancer to evaluate the tumor inhibition effect of CIR...

Prostate cancer (PCa) is a malignant disorder of prostate gland being asymptomatic in early stages and high metastatic potential in advanced stages. The chemotherapy and surgical resection have provided favourable prognosis of PCa patients, but advanced and aggressive forms of PCa including CRPC and AVPC lack response to therapy properly, and therefore, prognosis of patients is deteriorated. At the advanced stages, PCa cells do not respond to chemotherapy and radiotherapy in a satisfactory level, and therefore, therapy resistance is emerged...

BACKGROUND: The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues...

PURPOSE: Radiation induced pneumonitis (RIP) seriously limits the application of radiotherapy in the treatment of thoracic tumors, and its etiology and pathogenesis remain elusive. This study aims to elucidate the role of Ubiquitin-specific peptidase 11 (USP11) in the progression of RIP and the associated underlying mechanisms. METHODS AND MATERIALS: The changes of cytokines and infiltrated immune cells were detected by ELISA and IHC after exposed to 20 Gy X-ray with whole thorax irradiation...

Over half of patients with brain tumors experience debilitating and often progressive cognitive decline after radiotherapy treatment. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults, microglia can develop innate immune memory (IIM), which can either enhance (priming or training) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigate whether radiation affects the IIM of microglia by irradiating the brains of rats and later exposing them to a secondary inflammatory stimulus...

Radiological heart damage (RIHD) is damage caused by unavoidable irradiation of the heart during chest radiotherapy, with a long latency period and a progressively increasing proportion of delayed cardiac damage due to conventional doses of chest radiotherapy. There is a risk of inducing diseases such as acute/chronic pericarditis, myocarditis, delayed myocardial fibrosis and damage to the cardiac conduction system in humans, which can lead to myocardial infarction or even death in severe cases. This paper details the pathogenesis of RIHD and gives potential targets for treatment at the molecular and cellular level, avoiding the drawbacks of high invasiveness and immune rejection due to drug therapy, medical device implantation and heart transplantation...

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin...

Recent in vitro experiments showed that combined treatment with MHY1485, a low-molecular-weight compound, and X-ray irradiation significantly increased apoptosis and senescence in tumor cells, which was associated with oxidative stress, endoplasmic reticulum (ER) stress and p21 stabilization, compared to radiation treatment alone. However, evidence for MHY1485 treatment-mediated suppression of tumor growth in animals is still lacking. Furthermore, it has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can exert a favorable influence on the anti-cancer immune system...

Interest surrounding the effect of irradiation on immune activation has exponentially grown within the last decade. This includes work regarding mechanisms of the abscopal effect and the success achieved by combination of radiotherapy and immunotherapy. It is hypothesized that irradiation triggers the immune system to eliminate tumors by inducing tumor cells immunogenic cell death (ICD) in tumor cells. Activation of the ICD pathways can be exploited as an in situ vaccine. In this review, we provide fundamental knowledge of various forms of ICD caused by irradiation, describe the relationship between various cell death pathways and the immune activation effect driven by irradiation, and focus on the therapeutic value of exploiting these cell death programs in the context of irradiation...

Background: The role of senescent cells in the tumor microenvironment (TME) is usually bilateral, and diverse therapeutic approaches, such as radiotherapy and chemotherapy, can induce cellular senescence. Cellular interactions are widespread in the TME, and tumor cells reprogram immune cells metabolically by producing metabolites. However, how senescent cells remodel the metabolism of TME remains unclear. This study aimed to explore precise targets to enhance senescent cells-induced anti-tumor immunity from a metabolic perspective...