Related Experiment Videos
Natural cytotoxicity in lymphatic metastasis. II. In vivo studies with BSp73 variants differing in metastatic
Abstract:
The survival of cloned variants of the BSp73 tumor differing in susceptibility to natural killer (NK) and macrophage-mediated cytotoxicity in vitro was evaluated in syngeneic animals. The cytocidal effect was assayed by whole-body determination of (125I)5-iodo-2'-deoxyuridine (125IUdR) retention in intact animals and in animals depleted of phagocytes and/or radiation-sensitive lymphocytes. The following results were obtained: (1) In the peritoneal cavity, survival of the susceptible tumor cells (variant AS) was significantly higher in rats pretreated with radiation and silica than in untreated rats. (2) Cold target competition, response modification by C. parvum, and correlation of label excretion with survival of animals supported the notion that excretion rates of radioactivity were in fact determined by natural cytotoxicity in vivo. (3) Tumor cells resistant to natural cytotoxicity in vitro (variant ASML) were nevertheless killed in vivo (IP) by NK cells and macrophages. (4) Additional elements of tumor cell destruction were active upon IV injection of both AS- and ASML-derived cells, since rapid label excretion was observed irrespective of irradiation and silica treatment or addition of excess unlabeled competitor cells. The apparent increase in susceptibility of ASML cells in vivo might be due to a shift in phenotype induced by microenvironmental factors. No evidence was gained that differences in metastatic capacity exhibited by the variants might relate to differential action of natural cytotoxicity on these cells.
Insights
Tumor cell variants showed different survival rates in vivo, influenced by natural killer (NK) cells and macrophages. In vivo conditions, particularly microenvironmental factors, altered tumor cell susceptibility to immune responses.
Area of Science:
- Immunology
- Cancer Biology
- Tumor Microenvironment
Background:
- Cloned tumor variants (BSp73) exhibit differential susceptibility to natural killer (NK) and macrophage-mediated cytotoxicity in vitro.
- Understanding in vivo immune responses against tumor cells is crucial for cancer therapy.
Purpose of the Study:
- To evaluate the in vivo survival of cloned tumor variants with differing in vitro cytotoxic susceptibility.
- To investigate the roles of NK cells and macrophages in controlling tumor cell growth in vivo.
- To explore the influence of the tumor microenvironment on immune cell-mediated tumor cell destruction.
Main Methods:
- Assessing cytocidal effects using whole-body (125I)5-iodo-2'-deoxyuridine (125IUdR) retention in syngeneic animals.
- Employing depletion of phagocytes and/or radiation-sensitive lymphocytes to identify effector cells.
- Utilizing cold target competition and C. parvum treatment to analyze natural cytotoxicity in vivo.
Main Results:
- Susceptible tumor cells (variant AS) showed higher survival in vivo when phagocytes and NK cells were depleted.
- Tumor cells resistant in vitro (variant ASML) were killed in vivo, suggesting additional cytotoxic mechanisms.
- Intravenous injection of tumor cells led to rapid destruction regardless of immune cell status, indicating potent in vivo clearance.
- Microenvironmental factors may induce phenotypic shifts, increasing tumor cell susceptibility in vivo.
Conclusions:
- In vivo tumor cell destruction involves NK cells and macrophages, but is also influenced by other factors.
- The tumor microenvironment plays a significant role in modulating tumor cell susceptibility to immune surveillance.
- Differential metastatic capacity of tumor variants was not directly linked to natural cytotoxicity differences.