scholarly journals P04.34 Low-dose irradiation increases recruitment and effector function of tumor-specific T cells in experimental gliomas

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii286-iii286
Author(s):  
X Zhang ◽  
K Sahm ◽  
J Sonner ◽  
K Jähne ◽  
M Breckwoldt ◽  
...  
1981 ◽  
Vol 78 (3) ◽  
pp. 1809-1812 ◽  
Author(s):  
A. F. Tilkin ◽  
N. Schaaf-Lafontaine ◽  
A. Van Acker ◽  
M. Boccadoro ◽  
J. Urbain

2002 ◽  
Vol 8 (6) ◽  
pp. 469-474 ◽  
Author(s):  
K A Karls ◽  
P W Denton ◽  
R W Melvold

Two histocompatible substrains of BALB/c mice (BALB/cByJ, BALB/cAnNCr) are resistant and susceptible, respectively, to Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) - a model for viral etiology of human multiple sclerosis. BALB/cByJ mice become susceptible following low-dose irradiation given prior to infection. Resistance is restored by adoptive transfer of CD8+ (but not CD4+) splenic T cells from infected, unirradiated BALB/cByJ donors. In contrast, resistance is conferred to BALB/cAnNCr mice by adoptive transfer of either CD4+ or CD8+ T cells from resistant BALB/cByJ donors. T cells from BALB/cAnNCr mice cannot confer protection. To integrate these two observations, we hypothesized that the BALB/cAnNCr mice possess precursors of the regulatory CD8+ T cells, but fail to activate them because they lack a critical CD4+ T-cell subpopulation. We tested this model using serial transfers. The transfer of CD4+ T cells from the BALB/cByJ to the BALB/cAnNCr mice permitted development of BALB/cAnNCr CD8+ T cells that, in turn, provided resistance when transferred into susceptible recipients. The BALB/cByJ CD4+ T cells, which activated the CD8+ cells, were sensitive to low-dose irradiation, unlike CD4+ T cells involved in the later inflammatory demyelination. Thus, susceptibility of BALB/cAnNCr mice is due to a defective/absent CD4+ T -cell subset acting immediately after infection.


2006 ◽  
Vol 82 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Gregor Warnecke ◽  
Murat Avsar ◽  
Manuel Morancho ◽  
Carsten Peters ◽  
Stefanie Thissen ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1126
Author(s):  
Kyung-Hee Song ◽  
Seung-Youn Jung ◽  
Jeong-In Park ◽  
Jiyeon Ahn ◽  
Jong-Kuk Park ◽  
...  

Low-dose irradiation (LDI) has recently been shown to have various beneficial effects on human health, such as on cellular metabolic activities, DNA repair, antioxidant activity, homeostasis potency, and immune activation. Although studies on the immunogenic effects of LDI are rapidly accumulating, clinical trials for cancer treatment are considered premature owing to the lack of available preclinical results and protocols. Here, we aim to investigate anti-tumor and anti-metastatic effects of whole-body LDI in several tumor-bearing mouse models. Mice were exposed to single or fractionated whole-body LDI prior to tumor transplantation, and tumor growth and metastatic potential were determined, along with analysis of immune cell populations and expression of epithelial–mesenchymal transition (EMT) markers. Whole-body fractionated-LDI decreased tumor development and lung metastasis not only by infiltration of CD4+, CD8+ T-cells, and dendritic cells (DCs) but also by attenuating EMT. Moreover, a combination of whole-body LDI with localized high-dose radiation therapy reduced the non-irradiated abscopal tumor growth and increased infiltration of effector T cells and DCs. Therefore, whole-body LDI in combination with high-dose radiation therapy could be a potential therapeutic strategy for treating cancer.


Circulation ◽  
1996 ◽  
Vol 93 (3) ◽  
pp. 529-536 ◽  
Author(s):  
John R. Laird ◽  
Andrew J. Carter ◽  
William M. Kufs ◽  
Timothy G. Hoopes ◽  
Andrew Farb ◽  
...  

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


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