Abscopal Effect of Partial Versus Whole Tumor Irradiation With Anti-CD40 in Pancreas and Lung Tumor Mouse Models

2020 ◽  
Vol 108 (3) ◽  
pp. e550
Author(s):  
S. Yasmin-Karim ◽  
B. Ziberi ◽  
R. Mueller ◽  
N. Bih ◽  
M. Moreau ◽  
...  
Keyword(s):  
Mouse Models ◽  
Lung Tumor ◽  
Abscopal Effect ◽  
Tumor Irradiation

scholarly journals EGFR-targeted therapy results in dramatic early lung tumor regression accompanied by imaging response and immune infiltration in EGFR mutant transgenic mouse models

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54137-54156 ◽  
Author(s):  
Abhilash Venugopalan ◽  
Min-Jung Lee ◽  
Gang Niu ◽  
José Medina-Echeverz ◽  
Yusuke Tomita ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Lung Tumor ◽  
Tumor Regression ◽  
Transgenic Mouse Models ◽  
Immune Infiltration ◽  
Egfr Mutant ◽  
Imaging Response

scholarly journals The Oncogenic Potential of a Mutant TP53 Gene Explored in Two Spontaneous Lung Cancer Mice Models

2020 ◽  
Author(s):  
Julian Ramelow ◽  
Christopher Brooks ◽  
Li GaO ◽  
Abeer A Almiman ◽  
Terence M Williams ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Models ◽  
Human Lung ◽  
Lung Tumor ◽  
Mutant Gene ◽  
Genetic Mutation ◽  
Tumor Formation ◽  
Human Lung Cancer ◽  
Oncogenic Potential ◽  
Age Related

Abstract BackgroundLung cancer is the number one cancer killer worldwide. A major impediment to progress in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor suppressor gene TP53 are among the most common alterations in human lung cancers.MethodsPreviously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H.ResultsWe found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents.ConclusionsOncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune check point inhibitors or other therapeutic strategies in treatment of lung cancer.

Esophagus sparing with IMRT in lung tumor irradiation: An EUD-based optimization technique

2005 ◽  
Vol 63 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Olivier Chapet ◽  
Emma Thomas ◽  
Marc L. Kessler ◽  
Benedick A. Fraass ◽  
Randall K. Ten Haken
Keyword(s):  
Lung Tumor ◽  
Optimization Technique ◽  
Tumor Irradiation

scholarly journals Generating and grading the abscopal effect: proposal for comprehensive evaluation of combination immunoradiotherapy in mouse models

2017 ◽  
Vol 6 (S5) ◽  
pp. S892-S899 ◽  
Author(s):  
Daniel K. Ebner ◽  
◽  
Walter Tinganelli ◽  
Alexander Helm ◽  
Alessandra Bisio ◽  
...  
Keyword(s):  
Mouse Models ◽  
Comprehensive Evaluation ◽  
Abscopal Effect

scholarly journals The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models

2020 ◽  
Author(s):  
Julian Ramelow ◽  
Christopher Brooks ◽  
Li GaO ◽  
Abeer A Almiman ◽  
Terence M Williams ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Models ◽  
Human Lung ◽  
Lung Tumor ◽  
Mutant Gene ◽  
Genetic Mutation ◽  
Tumor Formation ◽  
Human Lung Cancer ◽  
Oncogenic Potential ◽  
Age Related

Abstract Background: Lung cancer is the number one cancer killer worldwide. A major impediment to progress in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor suppressor gene TP53 are among the most common alterations in human lung cancers. Methods: Previously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H. Results: We found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents. Conclusions: Oncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune check point inhibitors or other therapeutic strategies in treatment of lung cancer.

scholarly journals Radiation Exposure–Induced Changes in the Immune Cells and Immune Factors of Mice With or Without Primary Lung Tumor

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092674 ◽  
Author(s):  
Shuxian Pan ◽  
Jingjie Wang ◽  
Anqing Wu ◽  
Ziyang Guo ◽  
Ziyang Wang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Lung Tumor ◽  
Small Animal ◽  
Tumor Formation ◽  
Mouse Serum ◽  
Tumor Irradiation ◽  
Tumor Mouse Model ◽  
Primary Lung Tumor ◽  
The Right ◽  
Induced Changes

Recent studies have demonstrated that radiation activates in situ antitumor immunity and consequently induced a synergistic effect of radiotherapy and immunotherapy. However, studies related to radiation-induced changes in immune system of tumor-bearing mice are limited, which are of great significance to improve the efficacy of radioimmunotherapy. In this study, we first established a primary lung tumor mouse model using urethane. Then part of the right lung of the mouse was exposed to X-ray irradiation with a computed tomography–guided small animal irradiator and the changes of immune cells in both peripheral blood and spleen were determined by flow cytometry. Besides, the levels of both cytokines and immunoglobulins in mouse serum were detected by a protein chip. We found that B lymphocytes increased while CD8+ T lymphocytes reduced significantly. Interleukin-3 (IL-3), IL-6, regulated upon activation, normally T-expressed, and presumably secreted factor (RANTES), and vascular endothelial growth factor (VEGF) were found to be decreased after tumor formation, and the similar results have also been observed with kappa, IgG3, IgE, IgM, and IgG2a. After irradiation, lower concentrations of IgD, kappa, and IgM were found in the serum. Our findings indicate that localized tumor irradiation caused some obvious changes like inhibiting the ability of innate immunity, and these changes may be useful in predicting prognosis.

scholarly journals Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000867
Author(s):  
Zachary S Buchwald ◽  
Tahseen H Nasti ◽  
Judong Lee ◽  
Christiane S Eberhardt ◽  
Andres Wieland ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Subset ◽  
Abscopal Effect ◽  
Tumor Irradiation ◽  
Programmed Death ◽  
Draining Lymph Node ◽  
Tumor Draining Lymph Node ◽  
A Site ◽  
Lcmv Infection

BackgroundRadiotherapy (RT) has been shown to stimulate an antitumor immune response in irradiated tumors as well as unirradiated distant sites (abscopal effect). Previous studies have demonstrated a role for the tumor-draining lymph node (LN) in mediating an anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) stimulated antitumor immune response. Here, we investigated whether the LN is also important in mediating a RT alone stimulated abscopal response.MethodsWe used a subcutaneous modified B16F10 flank tumor model injected bilaterally. Our B16F10 cell line has an inserted viral glycoprotein which facilitated identification of tumor-specific T-cells. RT was directed at one flank tumor alone or one flank tumor and the tumor-draining LN. We evaluated response by tumor growth measurements and flow cytometry of both tumor-infiltrating and LN T-cells.ResultsWe show that local tumor irradiation improves distant tumor control (abscopal effect). Depletion of CD8+ T-cells significantly reduced this abscopal response. We have previously shown, in a chronic lymphocytic choriomeningitis virus (LCMV) infection, that the T-cell proliferative burst following blockade of PD-1/L1 is provided by a ‘stem-like’ CD8+ T-cell subset which then differentiate into terminally differentiated effectors. These terminally differentiated effectors have the potential to kill virally infected or tumor cells following PD-1/L1 blockade. In the chronic LCMV infection, stem-like CD8+ T-cells were found exclusively in secondary lymphoid organs. Similarly, here we found these cells at high frequencies in the tumor-draining LN, but at low frequencies within the tumor. The effect of RT on this T-cell subset in unknown. Interestingly, tumor irradiation stimulated total CD8+ and stem-like CD8+ T-cell proliferation in the LN. When the LN and the tumor were then targeted with RT, the abscopal effect was reduced, and we found a concomitant reduction in the number of total tumor-specific CD8+ T-cells and stem-like CD8+ T-cells in both the irradiated and unirradiated tumor.ConclusionsThese correlative results suggest the tumor-draining LN may be an important mediator of the abscopal effect by serving as a stem-like CD8+ T-cell reservoir, a site for stem-like T-cell expansion, and a site from which they can populate the tumor.

scholarly journals A Beam-Angle-Selection Method to Improve Inter-Fraction Motion Robustness for Lung Tumor Irradiation With Passive Proton Scattering

2020 ◽  
Vol 19 ◽  
pp. 153303382094805
Author(s):  
Yawei Zhang ◽  
Meng Wei Ho ◽  
Zuofeng Li
Keyword(s):  
Proton Beam ◽  
Lung Tumor ◽  
Patient Specific ◽  
Beam Angle ◽  
Target Dose ◽  
Internal Target Volume ◽  
Equivalent Thickness ◽  
Tumor Irradiation ◽  
The Impact ◽  
Planning Ct

In terms of dose distribution, protons are more sensitive to range variations than photons due to their unique properties. The aim of this study was to develop a method to identify patient-specific robust proton beam angles for lung tumor irradiation by investigating the association between water equivalent thickness (WET) variation and inter-fraction motion-induced target dose degradation. Using 3-dimensional computed tomography (3D-CT) images, the impact of WET variations on the target dose coverage of a series of coplanar proton beams was evaluated for 4 patients with lung cancer. Using ray tracing, WET maps, or WET baseline, were estimated for the internal target volume (ITV) at every 5° gantry interval in the axial plane. After calculating the WET baseline, the planning CT was shifted 5 mm in each anterior-posterior (AP), superior-inferior (SI), and left-right (LR) direction, yielding a total of 6 shifted CTs, and differential WET maps between the planning CT and each shifted CT were calculated. Target dose differences were associated with the average WET change between the original planning CT and the shifted CTs for all 360° gantry rotation beams. Target and OAR dose metrics in the ΔWET-guided plans were compared with those of the clinical plans. The WET variation maps showed areas of both high and low WET variations, with overall similar patterns yet individual differences reflecting tumor position differences. For all 4 patients investigated in this study, the coplanar plans demonstrated a strong correlation between WET changes and ITV dose reductions. Target dose coverage was more stable with the ΔWET-guided plan while OAR doses were comparable to the clinical plan. The WET variation maps have been used in this pilot study to identify proton beam angles that are either sensitive or robust to WET changes in proton passive scattering. This work demonstrates the feasibility of using WET variation maps to assist the planner in inter-fraction motion-robust proton beam angle selection.

Sign in / Sign up

Export Citation Format

Share Document