Induction of human autologous cytotoxic T lymphocytes against minced tissues of glioblastoma multiforme

1996 ◽  
Vol 84 (2) ◽  
pp. 258-263 ◽  
Author(s):  
Hideo Tsurushima ◽  
Shu Qin Liu ◽  
Koji Tsuboi ◽  
Yoshihiko Yoshii ◽  
Tadao Nose ◽  
...  

✓ The authors induced autologous cytotoxic T lymphocytes (CTLs) directly from peripheral blood lymphocytes by preparing a coculture of minced tissue fragments of glioblastoma multiforme (GBM) with interleukins-1, -2, -4, and -6 and interferon-g in RHAMa medium containing 5% autologous plasma for 2 weeks. At the end of this period, the frequencies of CD3+, CD4+, CD8+, and CD16+ lymphocytes were 95% to 99%, 40% to 62%, 37% to 38%, and 0.2%, respectively. The lymphocytes killed 82% to 100% of the GBM cells within 48 hours at an effector-to-target cell ratio of 1.67, whereas in a separate coculture, autologous lymphokine-activated killer (LAK) cells killed only 33% of GBM cells under the same conditions. The lymphocytes showed no cytotoxicity against LAK-sensitive Daudi cells, natural killer—sensitive K562 cells or autologous fibroblasts grown from the brain tumor, although they did show slight cytotoxicities against allogeneic GBM cell lines. These results lead the authors to suggest that the lymphocyte population contains specific CTLs for autologous brain tumor cells and that these CTLs could be effective in adoptive immunotherapy to combat brain tumor.

1973 ◽  
Vol 38 (5) ◽  
pp. 631-634 ◽  
Author(s):  
Sayed El-Gindi ◽  
Mamdouh Salama ◽  
Mokhtar El-Henawy ◽  
Said Farag

✓ Two cases of occipital glioblastoma multiforme are reported in which a metastatic lesion involving the cervical lymph nodes on the side of the previous craniotomy was verified during life. This suggests to the authors that the brain tumor metastasized via lymphatic channels.


1992 ◽  
Vol 77 (5) ◽  
pp. 757-762 ◽  
Author(s):  
Frank P. Holladay ◽  
Teresa Heitz ◽  
Gary W. Wood

✓ Specific immune responses against malignant brain tumors have been difficult to demonstrate. Moreover, immunotherapy has met with little success, despite using lymphocytes with high levels of cytotoxicity against brain tumor cells. Lymphokine-activated killer (LAK) cells that nonspecifically kill brain tumor cells are produced by stimulating resting precursors with high concentrations of interleukin-2 (IL-2). Cytotoxic T lymphocytes that specifically kill brain tumor cells are produced by stimulating antigen receptor-positive immune-cell precursors with tumor cells. In an attempt to gain insight into immune cell function against brain tumors, the present study compared the in vitro and in vivo activities of LAK cells and cytotoxic T lymphocytes produced against RT2, a fast-growing rat glioma cell line. Lymphokine-activated killer cells were produced by stimulating normal rat spleen cells with 1000 units of IL-2, and RT2-specifie cytotoxic T lymphocytes were produced by priming them in vivo with RT2 and Corynebacterium parvum and restimulating primed spleen cells with RT2 in vitro. Lymphokine-activated killer cells were highly cytotoxic for a panel of syngeneic and allogeneic brain tumor and non-brain tumor target cells, including RT2, as measured in a 4-hour 51Cr release assay. Cytotoxic T lymphocytes were highly cytotoxic only for syngeneic brain tumor target cells. Lymphokine-activated killer cells and cytotoxic T lymphocytes were tested for in vivo antitumor activity against intracerebral RT2 by intravenous adoptive transfer of activated lymphocytes. Untreated rats died in approximately 2 weeks. Lymphokine-activated killer cells plus IL-2 failed to affect survival when treatment was initiated as early as 1 day following tumor inoculation. Cytotoxic T lymphocytes and IL-2 administered as late as Day 5 rejected progressing intracerebral tumor. Thus, although both cytotoxic T lymphocytes and LAK cells exhibited high levels of in vitro killing of glioma cells, only cytotoxic T lymphocytes rejected progressing intracerebral tumors.


1986 ◽  
Vol 64 (1) ◽  
pp. 114-117 ◽  
Author(s):  
Steven K. Jacobs ◽  
Debra J. Wilson ◽  
Paul L. Kornblith ◽  
Elizabeth A. Grimm

✓ Culture of peripheral blood lymphocytes (PBL) from brain-tumor patients with recombinant interleukin-2 (IL-2) results in the activation of lymphokine-activated killer cells (LAK) with the capacity to lyse autologous and allogeneic glioblastoma. In this study, PBL obtained from brain-tumor patients were cultured with or without IL-2 for 3 to 7 days and then tested for their ability to lyse target cells in a 4-hour chromium release cytotoxicity assay. The PBL were drawn 1 to 2 weeks following operative tumor debulking. Cells used as targets included fresh brain-tumor cells obtained at the time of craniotomy, fresh brain-tumor cells grown from 1 to 3 weeks in tissue culture, fresh autologous PBL, and allogeneic glioblastoma cells grown in tissue culture. Peripheral blood lymphocytes from brain-tumor patients that were cultured without IL-2 did not significantly lyse autologous or allogeneic glioblastoma. However, when these PBL were cultured with IL-2, LAK were generated which produced marked lysis of autologous as well as allogeneic tissue-culture glioblastoma in all of eight cases. Significant lysis of autologous fresh tumor by patient LAK was observed in four of five experiments. By contrast, patient LAK did not kill autologous normal PBL. The ability to generate LAK was not influenced by the patient's age, previous therapy, or the administration of steroids.


1999 ◽  
Vol 91 (6) ◽  
pp. 1041-1044 ◽  
Author(s):  
Michael Sabel ◽  
Jörg Felsberg ◽  
Martina Messing-Jünger ◽  
Eva Neuen-Jacob ◽  
Jürgen Piek

✓ The authors report the case of a man who had suffered a penetrating metal splinter injury to the left frontal lobe at 18 years of age. Thirty-seven years later the patient developed a left-sided frontal tumor at the precise site of the meningocerebral scar and posttraumatic defect. Histological examination confirmed a glioblastoma multiforme adjacent to the dural scar and metal splinters. In addition, a chronic abscess from which Propionibacterium acnes was isolated was found within the glioma tissue. The temporal and local association of metal splinter injury with chronic abscess, scar formation, and malignant glioma is highly suggestive of a causal relationship between trauma and the development of a malignant brain tumor.


1978 ◽  
Vol 148 (6) ◽  
pp. 1458-1467 ◽  
Author(s):  
A McMichael

Cytotoxic T lymphocytes (CTL), specific for influenza A/X31 virus, were generated from human peripheral blood lymphocytes. These CTL lysed target cells that were infected with the same virus and that shared HLA A or B locus antigens. Minimal lysis was observed when HLA-D antigens were shared. Not all HLA A and B antigens were equally effective. Efficient lysis of target cells was seen when HLA A1, A3, B7, B8, B27 and BW21 were shared with the CTL, but when HLA A2 was the only shared antigen lysis was usually minimal. This deficiency in CTL function associated with HLA A2 was not absolute. It is suggested that the function of this antigen might be influenced by other surface molecules on the cell and in particular the other HLA products.


Sensor Review ◽  
2019 ◽  
Vol 39 (4) ◽  
pp. 473-487 ◽  
Author(s):  
Ayalapogu Ratna Raju ◽  
Suresh Pabboju ◽  
Ramisetty Rajeswara Rao

Purpose Brain tumor segmentation and classification is the interesting area for differentiating the tumorous and the non-tumorous cells in the brain and classifies the tumorous cells for identifying its level. The methods developed so far lack the automatic classification, consuming considerable time for the classification. In this work, a novel brain tumor classification approach, namely, harmony cuckoo search-based deep belief network (HCS-DBN) has been proposed. Here, the images present in the database are segmented based on the newly developed hybrid active contour (HAC) segmentation model, which is the integration of the Bayesian fuzzy clustering (BFC) and the active contour model. The proposed HCS-DBN algorithm is trained with the features obtained from the segmented images. Finally, the classifier provides the information about the tumor class in each slice available in the database. Experimentation of the proposed HAC and the HCS-DBN algorithm is done using the MRI image available in the BRATS database, and results are observed. The simulation results prove that the proposed HAC and the HCS-DBN algorithm have an overall better performance with the values of 0.945, 0.9695 and 0.99348 for accuracy, sensitivity and specificity, respectively. Design/methodology/approach The proposed HAC segmentation approach integrates the properties of the AC model and BFC. Initially, the brain image with different modalities is subjected to segmentation with the BFC and AC models. Then, the Laplacian correction is applied to fuse the segmented outputs from each model. Finally, the proposed HAC segmentation provides the error-free segments of the brain tumor regions prevailing in the MRI image. The next step is to extract the useful features, based on scattering transform, wavelet transform and local Gabor binary pattern, from the segmented brain image. Finally, the extracted features from each segment are provided to the DBN for the training, and the HCS algorithm chooses the optimal weights for DBN training. Findings The experimentation of the proposed HAC with the HCS-DBN algorithm is analyzed with the standard BRATS database, and its performance is evaluated based on metrics such as accuracy, sensitivity and specificity. The simulation results of the proposed HAC with the HCS-DBN algorithm are compared against existing works such as k-NN, NN, multi-SVM and multi-SVNN. The results achieved by the proposed HAC with the HCS-DBN algorithm are eventually higher than the existing works with the values of 0.945, 0.9695 and 0.99348 for accuracy, sensitivity and specificity, respectively. Originality/value This work presents the brain tumor segmentation and the classification scheme by introducing the HAC-based segmentation model. The proposed HAC model combines the BFC and the active contour model through a fusion process, using the Laplacian correction probability for segmenting the slices in the database.


2019 ◽  
Vol 12 (4) ◽  
pp. 466-480
Author(s):  
Li Na ◽  
Xiong Zhiyong ◽  
Deng Tianqi ◽  
Ren Kai

Purpose The precise segmentation of brain tumors is the most important and crucial step in their diagnosis and treatment. Due to the presence of noise, uneven gray levels, blurred boundaries and edema around the brain tumor region, the brain tumor image has indistinct features in the tumor region, which pose a problem for diagnostics. The paper aims to discuss these issues. Design/methodology/approach In this paper, the authors propose an original solution for segmentation using Tamura Texture and ensemble Support Vector Machine (SVM) structure. In the proposed technique, 124 features of each voxel are extracted, including Tamura texture features and grayscale features. Then, these features are ranked using the SVM-Recursive Feature Elimination method, which is also adopted to optimize the parameters of the Radial Basis Function kernel of SVMs. Finally, the bagging random sampling method is utilized to construct the ensemble SVM classifier based on a weighted voting mechanism to classify the types of voxel. Findings The experiments are conducted over a sample data set to be called BraTS2015. The experiments demonstrate that Tamura texture is very useful in the segmentation of brain tumors, especially the feature of line-likeness. The superior performance of the proposed ensemble SVM classifier is demonstrated by comparison with single SVM classifiers as well as other methods. Originality/value The authors propose an original solution for segmentation using Tamura Texture and ensemble SVM structure.


Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2352-2355 ◽  
Author(s):  
Masaki Yasukawa ◽  
Hideki Ohminami ◽  
Junko Arai ◽  
Yoshihito Kasahara ◽  
Yasushi Ishida ◽  
...  

We investigated the cytotoxicity mechanisms of alloantigen-specific human CD4+ and CD8+ cytotoxic T lymphocytes (CTLs) using cells from family members with the Fas gene mutation. Alloantigen-specific CD4+ and CD8+ CTL bulk lines and clones were generated from 2 individuals by stimulation of their peripheral blood lymphocytes with allogeneic Fas−/− or Fas+/− cell lines that were established from B-lymphocytes of a patient with Fas deficiency and her mother, respectively. Both CD4+ and CD8+CTL bulk lines and clones directed against allogeneic HLA antigens exerted cytotoxicity against Fas−/− and Fas+/− cells to almost the same degree. The cytotoxicity of CD4+ and CD8+ CTLs appeared to be Ca2+-dependent and was completely inhibited by concanamycin A, an inhibitor of perforin-mediated cytotoxicity. Messenger RNAs for the major mediators of CTL cytotoxicity, Fas ligand, perforin, and granzyme B were all detected in these CD4+CTLs with the use of the reverse transcriptase polymerase chain reaction. The majority of CD4+ CTL clones that showed Fas-independent cytotoxicity were TH0, as determined by their cytokine production profile. These data, obtained with the use of a novel experimental system, clearly show that the main pathway of cytotoxicity mediated by alloantigen-specific human CD4+as well as by CD8+ CTLs is granule exocytosis, and not the Fas/Fas ligand system.


2003 ◽  
Vol 33 (5) ◽  
pp. 1174-1182 ◽  
Author(s):  
Julie Cabarrocas ◽  
Jan Bauer ◽  
Eliane Piaggio ◽  
Roland Liblau ◽  
Hans Lassmann

2021 ◽  
Vol 35 (3) ◽  
pp. 223-233
Author(s):  
Roohi Sille ◽  
Tanupriya Choudhury ◽  
Piyush Chauhan ◽  
Durgansh Sharma

Brain tumor segmentation is an essential and challenging task because of the heterogeneous nature of neoplastic tissue in spatial and imaging techniques. Manual segmentation of the tumor in MRI images is prone to error and time-consuming tasks. An efficient segmentation mechanism is vital to the accurate classification and segmentation of tumorous cells. This study presents an efficient hierarchical clustering-based dense CNN approach for accurately classifying and segmenting the brain tumor cells in MRI images. The research focuses on improving the efficiency of the segmentation algorithms by considering the qualitative measures such as the dice score coefficient using quantitative parameters such as mean square error and peak signal to noise ratio. The experimental analysis states the efficacy and prominence of the proposed technique compared to other models are tabulated within the paper.


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