TAMI-46. FRIEND AND FOE: RADIATION THERAPY INCREASES GLIOBLASTOMA IMMUNE EVASION VIA EVS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi208-vi208
Author(s):  
Markus Schweiger ◽  
Bakhos Tannous
Keyword(s):  
Radiation Therapy ◽  
Immune Evasion ◽  
Tumor Regression ◽  
Therapeutic Strategies ◽  
Term Survival ◽  
Dynamic Composition ◽  
Initial Tumor ◽  
Novel Therapeutic Strategies ◽  
Primary Malignant Brain Tumor

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival is extremely rare. Radiation therapy (RT) leads to successful initial tumor regression but recurrence is inevitable. Previous studies have shown that ionizing radiation leads to a change of immune-related markers on tumor cells. Extracellular vesicles (EVs) are membranous structures secreted by nearly every cell and have been shown drive GBM progression by acting as multifunctional signaling complexes. Here, we show that radiation of GBM cells leads to an altered EV secretion/uptake dynamic, composition, and protein content. Furthermore, we show that EVs secreted by radiated GBM cells modulate the innate (microglia/macrophages) as well as adaptive (T-cells) immune response in the tumor microenvironment. We dissected a novel mechanism by which GBM evades the immune system via EVs following RT, pointing towards novel therapeutic strategies to prevent GBM recurrence.

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies

2021 ◽  
Vol 42 (03) ◽  
pp. 392-410
Author(s):  
Olawale Amubieya ◽  
Allison Ramsey ◽  
Ariss DerHovanessian ◽  
Gregory A. Fishbein ◽  
Joseph P. Lynch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Therapeutic Strategies ◽  
Term Survival ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Prevention And Treatment ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

AbstractThe primary factor that limits long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD continues to evolve. Consensus definitions of CLAD and the major CLAD phenotypes were recently updated and clarified, but it remains to be seen whether the current definitions will lead to advances in management or impact care. Understanding the potential differences in pathogenesis for each CLAD phenotype may lead to novel therapeutic strategies, including precision medicine. Recognition of CLAD risk factors may lead to earlier interventions to mitigate risk, or to avoid risk factors all together, to prevent the development of CLAD. Unfortunately, currently available therapies for CLAD are usually not effective. However, novel therapeutics aimed at both prevention and treatment are currently under investigation. We provide an overview of the updates to CLAD-related terminology, clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential strategies to treat and prevent CLAD.

scholarly journals A case of long-term disease control in a patient with disseminated melanoma with synchronous detection of multiple brain metastases

2018 ◽  
Vol 5 (4) ◽  
pp. 98-105
Author(s):  
M. I. Kurzhupov
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
Targeted Therapy ◽  
Clinical Case ◽  
Total Duration ◽  
Skin Melanoma ◽  
Synchronous Detection ◽  
Term Survival ◽  
Stage Of Diagnosis

The article presents clinical trials data of melanoma with brain metastasis and a clinical case of long-term survival of a patient with disseminated skin melanoma and synchronous multiple metastatic brain damage by controlling a tumor disease using modern antitumor treatment, including targeted therapy, immunotherapy, radiation therapy, radiosurgery and neurosurgery (at the stage of diagnosis). The total duration of life after detection of the disease is 22 months, with an expected 2-3 months.

scholarly journals Plasticity in early immune evasion strategies of a bacterial pathogen

2018 ◽  
Vol 115 (16) ◽  
pp. E3788-E3797 ◽  
Author(s):  
Quentin Bernard ◽  
Alexis A. Smith ◽  
Xiuli Yang ◽  
Juraj Koci ◽  
Shelby D. Foor ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Innate Immune ◽  
Serum Complement ◽  
Term Survival ◽  
Evasion Strategy ◽  
Innate Immune Evasion ◽  
Novel Therapeutic

Borrelia burgdorferiis one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy ofB. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.

scholarly journals Electrotransfer of IL-15/IL-15Rα Complex for the Treatment of Established Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3072
Author(s):  
Shawna A. Shirley ◽  
Cathryn G. Lundberg ◽  
Richard Heller
Keyword(s):  
Plasmid Dna ◽  
Tumor Regression ◽  
Important Determinant ◽  
Expression Profiles ◽  
Cell Infiltrate ◽  
Term Survival ◽  
Interleukin 15 ◽  
Ifn Γ ◽  
Low Levels

Gene electrotransfer (GET) is a safe, reliable, and effective method of delivering plasmid DNA (pDNA) to solid tumors. GET has been previously used to deliver interleukin-15 (IL-15) to mouse melanoma, resulting in long-term tumor regression and the survival of a percentage of treated animals after challenge. To enhance this effect, we evaluated modulating the expression levels of IL-15 and co-expressing its receptor, IL-15Rα. GET was used to deliver plasmids encoding IL-15 and IL-15Rα to established B16.F10 tumors on days 0, 4, and 7. Two delivery protocols that yielded different expression profiles were utilized. Mice that were tumor-free for 50 days were then challenged with B16.F10 cells on the opposite flank and monitored for an additional 50 days. The amount of IL-15 expressed and the presence or absence of IL-15Rα in the treated tumors did not significantly affect the tumor regression and long-term survival. Upon challenge, however, low levels of IL-15 were more protective and resulted in a greater production of anti-tumor cytokines such as IFN-γ and MIP-1β and a greater amount of CD11b+ and CD3e+ cells infiltrating tumors. While mice with high levels of IL-15 showed CD11b+ and CD3e+ cell infiltrate, there was a substantial presence of NK cells that was absent in other treated groups. We can conclude that the level of IL-15 expressed in tumors after GET is an important determinant of the therapeutic outcome, a finding that will help us finetune this type of therapy.

scholarly journals Long-term survival with tumor regression in androgen-induced liver tumors

Cancer ◽  
1985 ◽  
Vol 56 (11) ◽  
pp. 2622-2626 ◽  
Author(s):  
Geoffrey W. McCaughan ◽  
Michael J. Bilous ◽  
Neil D. Gallagher
Keyword(s):  
Liver Tumors ◽  
Tumor Regression ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Long-Term Survival in a Dog with Anaplastic Oligodendroglioma Treated with Radiation Therapy and CCNU

2012 ◽  
Vol 74 (11) ◽  
pp. 1517-1521 ◽  
Author(s):  
Daisuke HASEGAWA ◽  
Kazuyuki UCHIDA ◽  
Takayuki KUWABARA ◽  
Shunta MIZOGUCHI ◽  
Naoko YAYOSHI ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Anaplastic Oligodendroglioma ◽  
Term Survival ◽  
Long Term Survival
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