In vitro Interactions Between Tumor Cells and Immune Lymphoid Cells

Unprimed mouse spleen cells cultured in vitro on syngeneic tumor cell monolayers have been previously shown to become specifically sensitized and to mediate cytotoxicity against the same type of tumor cells. This complete in vitro system of cell-mediated response has been presently used to test the effect of a thymic humoral factor (THF) upon the differentiation process leading to the generation of specifically committed lymphocytes. Culture media were supplemented with 2% THF during either the sensitization or effector phase, or both phases of the reaction. Whereas the addition of THF during both phases or during sensitization only resulted in a significant increase in the cytotoxicity index, THF added during the effector phase was ineffective. The behavior of unsensitized spleen cells and of spleen cells sensitized against nonrelated transplantation antigens remained unmodified by THF. After showing that the entire reaction is mediated by lymphocytes of thymic origin, THF was directly tested on T or B spleen cells. It was found that only T cells reacted to THF by an increased cytotoxic capacity, while B cells remained inactive after addition of THF. It was therefore concluded that THF activates a postthymic population of lymphoid cells, transforming them into fully competent lymphocytes.

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Involvement of NK Cells against Tumors and Parasites

The International Journal of Biological Markers ◽

10.1177/172460080702200208 ◽

2007 ◽

Vol 22 (2) ◽

pp. 144-153 ◽

Cited By ~ 8

Author(s):

M. Papazahariadou ◽

G.I. Athanasiadis ◽

E. Papadopoulos ◽

I. Symeonidou ◽

M. Hatzistilianou ◽

...

Keyword(s):

Nk Cells ◽

Tumor Cells ◽

Cell Interaction ◽

Cytolytic Activity ◽

Lymphoid Cells ◽

Significant Activity ◽

Independent Manner ◽

Diverse Range ◽

Mediate Cytotoxicity

Host resistance against pathogens depends on a complex interplay of innate and adaptive immune mechanisms. Acting as an early line of defence, the immune system includes activation of neutrophils, tissue macrophages, monocytes, dendritic cells, eosinophils and natural killer (NK) cells. NK cells are lymphoid cells that can be activated without previous stimulation and are therefore like macrophages in the first line of defence against tumor cells and a diverse range of pathogens. NK cells mediate significant activity and produce high levels of proinflammatory cytokines in response to infection. Their cytotoxicity production is induced principally by monocyte-, macrophage- and dendritic cell-derived cytokines, but their activation is also believed to be cytokine-mediated. Recognition of infection by NK cells is accomplished by numerous activating and inhibitory receptors on the NK cells’ surface that selectively trigger the cytolytic activity in a major histocompability complex-independent manner. NK cells have trypanocidal activity of fibroblast cells and mediate direct destruction of extracellular epimastigote and trypomastigote forms of T. cruzi and T. lewisi in vitro; moreover, they kill plasmodia-infected erythrocytes directly through cell-cell interaction. This review provides a more detailed analysis of how NK cells recognize and respond to parasites and how they mediate cytotoxicity against tumor cells. Also the unique role of NK cells in innate immunity to infection and the relationship between parasites and carcinogenesis are discussed.

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Osteopontin Blockade Immunotherapy Increases Cytotoxic T Lymphocyte Lytic Activity and Suppresses Colon Tumor Progression

Cancers ◽

10.3390/cancers13051006 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1006

Author(s):

John D. Klement ◽

Dakota B. Poschel ◽

Chunwan Lu ◽

Alyssa D. Merting ◽

Dafeng Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Tumor Cells ◽

T Cell Activation ◽

Cell Activation ◽

Lymphoid Cells ◽

Colon Tumor ◽

Tumor Bearing

Human colorectal cancers are mostly microsatellite-stable with no response to anti-PD-1 blockade immunotherapy, necessitating the development of a new immunotherapy. Osteopontin (OPN) is elevated in human colorectal cancer and may function as an immune checkpoint. We aimed at elucidating the mechanism of action of OPN and determining the efficacy of OPN blockade immunotherapy in suppression of colon cancer. We report here that OPN is primarily expressed in tumor cells, myeloid cells, and innate lymphoid cells in human colorectal carcinoma. Spp1 knock out mice exhibit a high incidence and fast growth rate of carcinogen-induced tumors. Knocking out Spp1 in colon tumor cells increased tumor-specific CTL cytotoxicity in vitro and resulted in decreased tumor growth in vivo. The OPN protein level is elevated in the peripheral blood of tumor-bearing mice. We developed four OPN neutralization monoclonal antibodies based on their efficacy in blocking OPN inhibition of T cell activation. OPN clones 100D3 and 103D6 increased the efficacy of tumor-specific CTLs in killing colon tumor cells in vitro and suppressed colon tumor growth in tumor-bearing mice in vivo. Our data indicate that OPN blockade immunotherapy with 100D3 and 103D6 has great potential to be further developed for colorectal cancer immunotherapy and for rendering a colorectal cancer response to anti-PD-1 immunotherapy.

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CELLULAR IMMUNOABSORBENTS IN TRANSPLANTATION IMMUNITY

Journal of Experimental Medicine ◽

10.1084/jem.135.4.972 ◽

1972 ◽

Vol 135 (4) ◽

pp. 972-984 ◽

Cited By ~ 65

Author(s):

Gideon Berke ◽

Raphael H. Levey

Keyword(s):

Tumor Growth ◽

Tumor Cells ◽

Lymphoid Cells ◽

Target Cells ◽

Transplantation Immunity

Mouse lymphoid cells, sensitized against tumor allografts, can be deprived of the immunoreactive cells by in vitro absorption with specific fibroblast monolayers. Populations of lymphocytes so depleted are less effective in retarding tumor growth in vivo and in lysing tumor cells in vitro. Moreover, the adsorbed immunoreactive cells can be recovered specifically and are subsequently efficient in inhibiting tumor growth in vivo and in killing tumor cells in vitro. Further evidence is presented for the suggestion that the destruction of target cells in vitro by sensitized lymphoid cells is truly representative of the mode of destruction of grafted cells in vivo.

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REJECTION OF ASCITES TUMOR ALLOGRAFTS

Journal of Experimental Medicine ◽

10.1084/jem.136.6.1594 ◽

1972 ◽

Vol 136 (6) ◽

pp. 1594-1604 ◽

Cited By ~ 44

Author(s):

Gideon Berke ◽

Karen A. Sullivan ◽

Bernard Amos

Keyword(s):

Tumor Cells ◽

Intermediate Phase ◽

Lymphoid Cells ◽

Ascites Tumor ◽

Temperature Dependent ◽

51Cr Release ◽

Effector Cells ◽

Full Rate ◽

Initial Interaction

A pathway for cell-mediated tumor destruction in vitro by immune peritoneal exudate lymphoid cells has been proposed. The union of lymphocytes and tumor cells precedes the formation of an intermediate phase leading to lysis. The initial interaction is only partially temperature dependent. The cytolytic process per se is highly temperature dependent, being negligible at 25°C but proceeding rapidly at 37°C. 51Cr release from tumor cells is demonstrable within 10 min at 37°C and can be reversibly arrested by cooling. Once initiated, lysis is largely independent of additional interactions and continues at almost full rate for 30 min. The effector cells are not lysed and appear to be free to enter into further effector cycles.

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In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha

Journal of Hepatology ◽

10.1034/j.1600-0641.2000.033004601.x ◽

2000 ◽

Vol 33 (4) ◽

pp. 601-608 ◽

Cited By ~ 8

Author(s):

Shwu-Bin Lin ◽

Li-Ching Wu ◽

Siao-Ling Huang ◽

Hui-Lun Hsu ◽

Sung-Hwa Hsieh ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Tumor Cells ◽

Rat Liver ◽

Antisense Oligonucleotide ◽

Epithelial Tumor ◽

Kinase C ◽

Epithelial Tumor Cells

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Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Melatonin Research ◽

10.32794/mr11250042 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83-98 ◽

Cited By ~ 2

Author(s):

André De Lima Mota ◽

Bruna Vitorasso Jardim-Perassi ◽

Tialfi Bergamin De Castro ◽

Jucimara Colombo ◽

Nathália Martins Sonehara ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Tumor Growth ◽

Tumor Cells ◽

Carbonic Anhydrases ◽

In Vivo Models ◽

Ca Ix ◽

Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

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