Flow Cytometry Evaluation of Gap Junction-Mediated Intercellular Communication Between Cytotoxic T Cells and Target Tumor Cells

2020 ◽  
Author(s):  
Mariela Navarrete ◽  
Flavio Salazar-Onfray ◽  
Andrés Tittarelli
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Gap Junction ◽  
Tumor Cells ◽  
Intercellular Communication ◽  
Cytotoxic T Cells

scholarly journals Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells.

1976 ◽  
Vol 143 (3) ◽  
pp. 601-614 ◽  
Author(s):  
J W Schrader ◽  
G M Edelman
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Target Cell ◽  
Cytotoxic T Cells ◽  
Hybrid Origin ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Effector Cells

Cytotoxic T lymphocytes were generated in vitro against H-2 compatible or syngeneic tumor cells. In vitro cytotoxic activity was inhibited by specific anti-H2 sera, suggesting that H-2 antigens are involved in cell lysis. Two observations directly demonstrated the participation of the H-2 antigens on the tumor cells in their lysis by H-2-compatible T cells. First, coating of the H-2 antigens on the target tumor cell reduced the number of cells lysed on subsequent exposure to cytotoxic T cells. Second, when cytotoxic T cells were activated against an H-2 compatible tumor and assayed against an H-2-incompatible tumor, anti-H-2 serum that could bind to the target cell, but not to the cytotoxic lymphocyte, inhibited lysis. H-2 antigens were also shown to be present on the cytotoxic lymphocytes. Specific antisera reacting with these H-2 antigens, but not those of the target cell, failed to inhibit lysis when small numbers of effector cells were assayed against H-2-incompatible target cells or when effector cells of F1-hybrid origin and bearing two H-2 haplotypes were assayed against a tumor cell of one of the parental strains. These findings suggest that it is the H-2 antigens on the tumor cell and not those on the cytotoxic lymphocytes that are important in cell-mediated lysis of H-2-compatible tumor cells.

Cellular investigations

2013 ◽  
pp. 555-578
Author(s):  
Gavin P Spickett
Keyword(s):  
Flow Cytometry ◽  
Tissue Culture ◽  
T Cells ◽  
Bronchoalveolar Lavage ◽  
Cytotoxic T Cells ◽  
Cd40 Ligand ◽  
Regulatory Factors ◽  
Ligand Expression ◽  
Proliferation Assays ◽  
Protein Assays

Introduction Flow cytometry Tissue culture Proliferation assays Immunohistology Cytokine, chemokine, soluble protein assays Apoptosis assays Adhesion markers Bronchoalveolar lavage (BAL) studies CD40 ligand expression Complement membrane regulatory factors Cytokine and cytokine receptor measurement Cytotoxic T cells FOXP3 (regulatory T cells—IPEX syndrome) Genetic and protein studies...

scholarly journals Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3785-3791 ◽  
Author(s):  
PC de Bruin ◽  
JA Kummer ◽  
P van der Valk ◽  
P van Heerde ◽  
PM Kluin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Lymphoid Tissue ◽  
Cytotoxic T Cells ◽  
Granzyme B ◽  
Clinical Behavior ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Peripheral T Cell Lymphomas

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa- associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T- cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T- cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.

scholarly journals New insights in the biology of Hodgkin lymphoma

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 328-334 ◽  
Author(s):  
Ralf Küppers
Keyword(s):  
T Cells ◽  
B Cells ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Cell Gene Expression ◽  
Expression Program ◽  
Multiple Signaling ◽  
Cell Gene

Abstract The Hodgkin and Reed/Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (HL) and the lymphocyte-predominant tumor cells of nodular lymphocyte–predominant HL are both derived from germinal center B cells. HRS cells, however, have largely lost their B-cell gene-expression program and coexpress genes typical of various types of hematopoietic cells. Multiple signaling pathways show a deregulated activity in HRS cells. The genetic lesions involved in the pathogenesis of HL are only partly known, but numerous members and regulators of the NF-κB and JAK/STAT signaling pathways are affected, suggesting an important role for these pathways in HL pathogenesis. Some genetic lesions involve epigenetic regulators, and there is emerging evidence that HRS cells have undergone extensive epigenetic alterations compared with normal B cells. HRS and lymphocyte-predominant cells are usually rare in the lymphoma tissue, and interactions with other cells in the microenvironment are likely critical for HL pathophysiology. T cells represent a main population of infiltrating cells, and it appears that HRS cells both inhibit cytotoxic T cells efficiently and also receive survival signals from Th cells in direct contact with them.

Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells

2003 ◽  
Vol 107 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Mikinori Miyazaki ◽  
Yoshiki Akatsuka ◽  
Tetsuya Nishida ◽  
Nobuharu Fujii ◽  
Akio Hiraki ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Cytotoxic T Cells ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen

scholarly journals Next-Generation Immunotherapies to Improve Anticancer Immunity

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaoyao Shi ◽  
Katarzyna Tomczak ◽  
June Li ◽  
Joshua K. Ochieng ◽  
Younghee Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Cell Subset ◽  
Cytotoxic T Cell ◽  
Killer Cells

Checkpoint inhibitors are widely used immunotherapies for advanced cancer. Nonetheless, checkpoint inhibitors have a relatively low response rate, work in a limited range of cancers, and have some unignorable side effects. Checkpoint inhibitors aim to reinvigorate exhausted or suppressed T cells in the tumor microenvironment (TME). However, the TME contains various other immune cell subsets that interact to determine the fate of cytotoxic T cells. Activation of cytotoxic T cells is initiated by antigen cross-presentation of dendritic cells. Dendritic cells could also release chemokines and cytokines to recruit and foster T cells. B cells, another type of antigen-presenting cell, also foster T cells and can produce tumor-specific antibodies. Neutrophils, a granulocyte cell subset in the TME, impede the proliferation and activation of T cells. The TME also consists of cytotoxic innate natural killer cells, which kill tumor cells efficiently. Natural killer cells can eradicate major histocompatibility complex I-negative tumor cells, which escape cytotoxic T cell–mediated destruction. A thorough understanding of the immune mechanism of the TME, as reviewed here, will lead to further development of more powerful therapeutic strategies. We have also reviewed the clinical outcomes of patients treated with drugs targeting these immune cells to identify strategies for improvement and possible immunotherapy combinations.

scholarly journals Modelling cancer immunomodulation using epithelial organoid cultures

2018 ◽  
Author(s):  
Yotam E. Bar-Ephraim ◽  
Kai Kretzschmar ◽  
Priyanca Asra ◽  
Evelien de Jongh ◽  
Kim E. Boonekamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
T Cells ◽  
Epithelial Cell ◽  
Differential Expression ◽  
Cytotoxic T Cells ◽  
Transcriptional Profiling ◽  
Cell Killing ◽  
Organoid Cultures

Here we utilize organoid technology to study immune-cancer interactions and assess immunomodulation by colorectal cancer (CRC). Transcriptional profiling and flow cytometry revealed that organoids maintain differential expression of immunomodulatory molecules present in primary tumours. Finally, we established a method to model antigen-specific epithelial cell killing and cancer immunomodulation in vitro using CRC organoids co-cultured with cytotoxic T cells (CTLs).

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