scholarly journals D-MT Prompts the Anti-Tumor Effect of Oxaliplatin by Inhibiting IDO Expression in a Mouse Model of Colon Cancer

2020 ◽  
Author(s):  
Tiesuo Zhao ◽  
Yongxi Zhang ◽  
Wenyan Fan ◽  
Jing Guo ◽  
Weiwei Ren ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Tumor Growth ◽  
Malignant Tumors ◽  
Cell Infiltration ◽  
Indoleamine Dioxygenase ◽  
Growth And Survival ◽  
Tumor Bearing ◽  
T Cell Infiltration ◽  
Tumor Tissues

Abstract BackgroundColon cancer is one of the most common malignant tumors in the digestive system. Although oxaliplatin, a chemotherapy drug, has been clinically used to treat colon cancer, its therapeutic effect is unsatisfactory. MethodsIn the present work, it has been proved that indoleamine dioxygenase 2,3 (IDO), an immune checkpoint, is a result of tolerance to chemotherapy. Herein, the anti-tumor effect of treatment with oxaliplatin and D-MT, an IDO inhibitor, on the mice was observed by recording the tumor growth and survival of the mice, and detecting T cell infiltration in tumor tissues and the ratios of immune cells in the spleen by corresponding methods. ResultsWe found that the combination of oxaliplatin and D-MT significantly inhibited tumor growth, prolonged the survival of tumor-bearing mice, increased the cell apoptosis. More importantly, the combination treatment increased the ratios of CD4+ T, CD8+ T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues. ConclusionThis study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance.

scholarly journals 49 In situ phenotypic analysis of T cells in the tumor microenvironment of a pre-clinical model of non-small cell lung cancer (NSCLC) by tissue sectioning and whole-mount immunofluorescence imaging

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A52-A52
Author(s):  
Elen Torres ◽  
Stefani Spranger
Keyword(s):  
T Cells ◽  
Spatial Distribution ◽  
T Cell ◽  
Spatial Location ◽  
Cell Infiltration ◽  
Cell Populations ◽  
Tumor Bearing ◽  
T Cell Infiltration ◽  
Volume Imaging ◽  
Whole Mount

BackgroundUnderstanding the interactions between tumor and immune cells is critical for improving current immunotherapies. Pre-clinical and clinical evidence has shown that failed T cell infiltration into lung cancer lesions might be associated with low responsiveness towards checkpoint blockade.1 For this reason, it is necessary to characterize not only the phenotype of T cells in tumor-bearing lungs but also their spatial location in the tumor microenvironment (TME). Multiplex immunofluorescence staining allows the simultaneous use of several cell markers to study the state and the spatial location of cell populations in the tissue of interest. Although this technique is usually applied to thin tissue sections (5 to 12 µm), the analysis of large tissue volumes may provide a better understanding of the spatial distribution of cells in relation to the TME. Here, we analyzed the number and spatial distribution of cytotoxic T cells and other immune cells in the TME of tumor-bearing lungs, using both 12 µm sections and whole-mount preparations imaged by confocal microscopy.MethodsLung tumors were induced in C57BL/6 mice by tail vein injection of a cancer cell line derived from KrasG12D/+ and Tp53-/- mice. Lung tissue with a diverse degree of T cell infiltration was collected after 21 days post tumor induction. Tissue was fixed in 4% PFA, followed by snap-frozen for sectioning. Whole-mount preparations were processed according to Weizhe Li et al. (2019) 2 for tissue clearing and multiplex volume imaging. T cells were labeled with CD8 and FOXP3 antibodies to identify cytotoxic or regulatory T cells, respectively. Tumor cells were labeled with a pan-Keratin antibody. Images were acquired using a Leica SP8 confocal microscope. FIJI3 and IMARIS were used for image processing.ResultsWe identified both cytotoxic and regulatory T cell populations in the TME using thin sections and whole-mount. However, using whole-mount after tissue clearing allowed us to better evaluate the spatial distribution of the T cell populations in relation to the tumor structure. Furthermore, tissue clearance facilitates the imaging of larger volumes using multiplex immunofluorescence.ConclusionsAnalysis of large lung tissue volumes provides a better understanding of the location of immune cell populations in relation to the TME and allows to study heterogeneous immune infiltration on a per-lesion base. This valuable information will improve the characterization of the TME and the definition of cancer-immune phenotypes in NSCLC.ReferencesTeng MW, et al., Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 2015;75(11): p. 2139–45.Li W, Germain RN, and Gerner MY. High-dimensional cell-level analysis of tissues with Ce3D multiplex volume imaging. Nat Protoc 2019;14(6): p. 1708–1733.Schindelin J, et al, Fiji: an open-source platform for biological-image analysis. Nat Methods 2012;9(7): p. 676–82.

scholarly journals Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Man-Chin Chen ◽  
Christian Ronquillo Pangilinan ◽  
Che-Hsin Lee
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Cell Infiltration ◽  
Tumor Immune Escape ◽  
Programmed Death Ligand 1 ◽  
T Cell Infiltration ◽  
Programmed Death

Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

scholarly journals Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e73684 ◽  
Author(s):  
Andrew Crowe ◽  
Connie Jackaman ◽  
Katie M. Beddoes ◽  
Belinda Ricciardo ◽  
Delia J. Nelson
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals CD8+ T cell infiltration in breast and colon cancer: A histologic and statistical analysis

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190158 ◽  
Author(s):  
James Ziai ◽  
Houston N. Gilbert ◽  
Oded Foreman ◽  
Jeffrey Eastham-Anderson ◽  
Felix Chu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Statistical Analysis ◽  
T Cell ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo

2020 ◽  
Vol 8 (2) ◽  
pp. e001673
Author(s):  
Brittany L Bunch ◽  
Jennifer Morse ◽  
Sarah Asby ◽  
Jamie Blauvelt ◽  
Ahmet M Aydin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cellular Therapy ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Tumor Cell Line ◽  
Cell Infiltration ◽  
T Cell Infiltration

BackgroundThe therapeutic armamentarium of bladder cancer has been recently enriched with the introduction of new therapies including immune checkpoint inhibitors, receptor tyrosine kinase inhibitors and antibody drug conjugates, however treatment responses and duration of responses are still less than expected. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated by successful expansion of tumor reactive T cells from human bladder tumors.MethodsA model system using OT-I T cells and an ovalbumin expressing MB49 tumor cell line (MB49OVA) was developed to study ACT in bladder cancer. Systemic ACT-treated mice were given T cells intravenously after lymphodepleting chemotherapy and followed by interleukin (IL)-2 administration. Intravesical ACT treated mice were given T cells directly into the bladder, without chemotherapy or IL-2. TILs were isolated from MB49 orthotopic tumors and expanded ex vivo in IL-2. Immune cell infiltrates were analyzed by flow cytometry. T cell infiltration was studied using a CXCR3 blocking antibody.ResultsSystemic ACT-treated mice had a decrease in tumor growth, increase in T cell infiltration and long-term immune protection compared with control-treated mice. OT-I T cells delivered intravesically were able to control tumor growth without lymphodepleting chemotherapy or IL-2 in MB49OVA orthotopic tumors. Intravesical delivery of TIL expanded from MB49 tumors was also able to decrease tumor growth in mice with MB49 orthotopic tumors. Blocking CXCR3 on OT-I T cells prior to intravesical delivery decreased T cell infiltration into the tumor and prevented the control of tumor growth.ConclusionsThis study demonstrates how TIL therapy can be used in treating different stages of bladder cancer.

scholarly journals Vitamin D Controls Tumor Growth and CD8+ T Cell Infiltration in Breast Cancer

2019 ◽  
Vol 10 ◽  
Author(s):  
Esma Karkeni ◽  
Stéphanie O. Morin ◽  
Berna Bou Tayeh ◽  
Armelle Goubard ◽  
Emmanuelle Josselin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
T Cell ◽  
Tumor Growth ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals Lack of MHC class II molecules favors CD8+T-cell infiltration into tumors associated with an increased control of tumor growth

2017 ◽  
Vol 7 (3) ◽  
pp. e1404213 ◽  
Author(s):  
Nada Chaoul ◽  
Alexandre Tang ◽  
Belinda Desrues ◽  
Marine Oberkampf ◽  
Catherine Fayolle ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Mhc Class Ii ◽  
Cd8 T Cell ◽  
Class Ii ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Mhc Class Ii Molecules
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