Characterization of IL-2-induced murine cells which exhibit ADCC activity

Cancer Immunol Immunother

1990

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Prostaglandins can inhibit the generation of lymphokine-activated killer (LAK) cells by interleukin-2 (IL-2) whereas indomethacin augmented the induction of LAK cells by inhibiting prostaglandin synthesis. In the present study we demonstrate that prostaglandin E2 substantially inhibited the generation of both LAK and antibody-dependent cellular cytotoxicity (ADCC) activity by IL-2. In addition, indomethacin enhanced the induction of LAK activity and ADCC in splenocytes exposed to IL-2 in vitro. The effect of indomethacin was dose-dependent, reaching an optimal effect at 1 microM when 100-1000 units/ml IL-2 were employed. The effect of indomethacin on the generation of ADCC was seen in cells taken from both tumor-bearing mice and normal mice. ADCC induced by IL-2 was augmented by culturing cells from the spleen, liver and lungs, in the presence of indomethacin. ADCC induced in the presence of IL-2 and indomethacin was mediated by cells that were mainly plastic non-adherent cells and expressed the asialo-GM1 glycolipid. The potential of indomethacin in combined therapy with cytokines and specific anti-tumor monoclonal antibodies is discussed.

Section: Methodsmentioning

confidence: 99%

Section: Isolation Of Cells From Various Organsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Indomethacin up-regulates the generation of lymphokine-activated killer-cell activity and antibody-dependent cellular cytotoxicity mediated by interleukin-2

Cancer Immunol Immunother

1990

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“…This hypothesis was analyzed in a direct fashion in studies in which class I antigen modulation on tumor cells was correlated with their immunogenicity and their ability to elicit a specific cell-mediated immune response [2,16,24,39,42,44,45]. The goal of such studies was to reveal practical methods to increase the host antitumor responses against weakly immunogenic tumors, as a step towards application in cancer therapy [5,19].…”

Section: Introductionmentioning

confidence: 99%

Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking

Ramakrishna

Cancer Immunol Immunother

Skornick

et al. 1993

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The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2',3'-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper.

“…Preparation of syngeneic spleen cells were from freshly removed spleens [15]. After smashing the spleen with the hub of a syringe, the cells were washed, the red blood cells lysed with a RBC-lysing buffer (Sigma), and the remaining cells washed twice in HBSS and resus pended in CM.…”

Section: Methodsmentioning

confidence: 99%

Surface Projection of Murine Major Histocompatibility Determinants Induced by Hydrostatic Pressure and Cytokines

Matsaev²,

Gelfand³

et al. 1996

Pathobiology

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Augmentation of surface presentation of the major histocompatibility complex (MHC) is a leading trend for preparation of tumor vaccines. Exposure of weakly immunogenic tumor cells, such as murine B16 melanoma, to hydrostatic pressure (P) in the presence of the membrane-impermeable protein crosslinker (CL) 2’,3’-adenosine dialdehyde, was previously shown to induce a substantial increase in surface presentation of MHC molecules. When B-16 melanoma cells, used here as a model, were first treated for 72 h with interferon-γ or tumor necrosis factor-α at concentrations of 10 and 100 units/ml, respectively, followed by application of pressure and cross-linking (PCL), the surface presentation of H2^b molecules increased by 40% compared to treatment with cytokines alone, and by up to 1,700% when compared to treatment with PCL alone. Neither P nor CL alone enhanced the MHC presentation when cells were pretreated with these cytokines. The changes in MHC observed after the cytokine treatment were transient and decayed within several hours. However, the changes induced by the sequential treatment with cytokines and PCL were sustained for at least 96 h post-PCL which is of prime importance for immunogenic expression. A series of analogous experiments in the presence of cycloheximide indicated that approximately 50% of the observed PCL-induced increase in MHC projection originates from protein synthesis while the other 50% corresponds to passive translocation of MHC compartments. B16 melanoma cells, modified by the sequential treatment of cytokines and PCL, proved to be substantially more immunogenic by an in vitro sensitization assay than cells treated by either one of these treatments alone. These results may provide a guideline for the preparation of tumor vaccines which could be applied in immunotherapy treatment of cancer.