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Colorectal cell line suppression of lymphokine activated killer cell generation is reversed by suramin
P D Allen1, D H Johnston, M G Macey
1Department of Haematology, London Hospital Medical College, Whitechapel, UK.
Abstract:
Progressive tumor growth is associated with a state of immunosuppression. One mode of immunosuppression is thought to be mediated by immunosuppressive factors of tumour origin. We have investigated in vitro the possibility that suramin could be used to blockade tumor derived suppressor factors and enhance the effectiveness of rhIL-2 therapy. These data show that factors derived from cultures of the colorectal carcinoma cell line LoVo suppressed the percentage of cells expressing the natural killer cell antigen CD56 in 92% of individuals and the cytotoxic T cell antigen CD8 in 77% of individuals tested from a panel of 13 normal healthy volunteers. Suramin at 200 micrograms/ml restored the percentage of cells expressing CD56 to levels higher than the control cultures and reduced the suppression in those expressing CD8 to non-significant levels. LoVo produced factors also suppressed the expression of the activation associated antigens CD25, CD71 and HLA-Dr with suramin restoring CD25 expression but not CD71 or HLA-Dr. Functional studies using 51Cr-release assays showed that LoVo produced factors could suppress cytotoxicity in 46% of individuals tested, and of these a reduction in suppression by suramin was demonstrated in 50% of individuals against Daudi target cells and 33% against K562 target cells.
Insights
Tumor-derived factors suppress immune cells, but suramin may block these effects. This study shows suramin can restore natural killer (NK) and cytotoxic T cell functions, potentially enhancing immunotherapy effectiveness.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Progressive tumor growth often leads to a suppressed immune state.
- Tumor-derived immunosuppressive factors are a key mechanism of this suppression.
- Enhancing immunotherapy, such as recombinant human interleukin-2 (rhIL-2) therapy, is a critical goal in cancer treatment.
Purpose of the Study:
- To investigate the potential of suramin to block tumor-derived suppressor factors in vitro.
- To determine if suramin can enhance the effectiveness of recombinant human interleukin-2 (rhIL-2) therapy.
- To assess suramin's impact on immune cell antigen expression and cytotoxic activity.
Main Methods:
- In vitro culture of colorectal carcinoma cell line (LoVo) to generate suppressor factors.
- Assessment of immune cell antigen expression (CD56, CD8, CD25, CD71, HLA-Dr) with and without suramin.
- Functional cytotoxicity assays (51Cr-release) to measure immune cell killing capacity.
Main Results:
- LoVo-derived factors suppressed natural killer (NK) cell antigen (CD56) and cytotoxic T cell antigen (CD8) expression in healthy volunteers.
- Suramin restored CD56 expression and reduced CD8 suppression.
- Suramin partially restored the expression of activation antigen CD25, but not CD71 or HLA-Dr.
- LoVo factors suppressed cytotoxicity in 46% of individuals; suramin reduced this suppression in 33-50% of cases.
Conclusions:
- Tumor-derived factors from LoVo cells induce immunosuppression by downregulating key immune cell antigens.
- Suramin demonstrates potential in blocking these tumor-derived immunosuppressive factors.
- Suramin may enhance immunotherapy by restoring immune cell function, warranting further investigation in clinical settings.