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New research indicates that toxins in Staphylococcus bacteria help malignant cells gain control over healthy cells in patients with cutaneous T-cell lymphoma (CTCL).
Investigators found that staphylococcal enterotoxin-A (SEA) induces STAT3 activation and IL-17 expression in malignant T cells via engagement of non-malignant CD4 T cells.
As STAT3 activation has been implicated in CTCL pathogenesis, the discovery suggests bacterial toxins play a key role in activating an oncogenic pathway in CTCL.
“We have gained important insight into the processes that activate cancer cells and make them grow,” said Niels Oedum, MD, of the University of Copenhagen in Denmark.
“[CTCL] patients’ frequent bacterial infections might not be a mere side effect of the disease. On the contrary, toxins in the bacteria actually ‘benefit’ cancer cells. Our next step is examining whether combatting infections can slow down the growth of cancer cells and thus stop the disease.”
Dr Oedum and his colleagues described their research in Blood.
The investigators knew that, in CTCL, CD4 T cells become malignant and turn parasitic on the rest of the immune system. In addition to using healthy cells to do their work for them, the malignant cells slowly destroy the skin’s immune defense mechanism.
The team’s new discoveries indicate that bacterial toxins in some patients enable malignant cells to send off signals that obstruct and change the immune defense mechanism, which would otherwise fight the malignant cells. What was believed to be an overly active immune defense mechanism could, in other words, turn out to be a malignant infection brought on by bacteria, which only worsens the disease.
Dr Oedum and his colleagues found that SEA-positive bacteria isolatated from the skin of CTCL patients stimulated activation of STAT3 and upregulation of IL-17 in malignant and non-malignant T cells.
Malignant T cells expressing an SEA non-responsive T-cell receptor V beta chain did not respond to SEA when cultured alone but exhibited STAT3 activation and IL-17 expression in co-cultures with SEA-responsive, non-malignant T cells.
The investigators found evidence to suggest the response is induced via IL-2Rg cytokines and a JAK3-dependent pathway in malignant T cells. The JAK3 inhibitor tofacitinib inhibited SEA-induced IL-17 production in co-cultures of malignant and non-malignant T cells.
Dr Oedum and his colleagues plan to continue their work investigating how bacteria might affect the balance between the immune defense mechanism and the disease in patients with CTCL.
In the long-term, the investigators’ aim is to understand how bacteria and their toxins can worsen CTCL, knowledge that may be used to develop new targeted treatments.
As only some of the bacteria produce toxins, the team said it will also be important to develop methods to determine which patients may benefit from treatment with antibiotics. 
New research indicates that toxins in Staphylococcus bacteria help malignant cells gain control over healthy cells in patients with cutaneous T-cell lymphoma (CTCL).
Investigators found that staphylococcal enterotoxin-A (SEA) induces STAT3 activation and IL-17 expression in malignant T cells via engagement of non-malignant CD4 T cells.
As STAT3 activation has been implicated in CTCL pathogenesis, the discovery suggests bacterial toxins play a key role in activating an oncogenic pathway in CTCL.
“We have gained important insight into the processes that activate cancer cells and make them grow,” said Niels Oedum, MD, of the University of Copenhagen in Denmark.
“[CTCL] patients’ frequent bacterial infections might not be a mere side effect of the disease. On the contrary, toxins in the bacteria actually ‘benefit’ cancer cells. Our next step is examining whether combatting infections can slow down the growth of cancer cells and thus stop the disease.”
Dr Oedum and his colleagues described their research in Blood.
The investigators knew that, in CTCL, CD4 T cells become malignant and turn parasitic on the rest of the immune system. In addition to using healthy cells to do their work for them, the malignant cells slowly destroy the skin’s immune defense mechanism.
The team’s new discoveries indicate that bacterial toxins in some patients enable malignant cells to send off signals that obstruct and change the immune defense mechanism, which would otherwise fight the malignant cells. What was believed to be an overly active immune defense mechanism could, in other words, turn out to be a malignant infection brought on by bacteria, which only worsens the disease.
Dr Oedum and his colleagues found that SEA-positive bacteria isolatated from the skin of CTCL patients stimulated activation of STAT3 and upregulation of IL-17 in malignant and non-malignant T cells.
Malignant T cells expressing an SEA non-responsive T-cell receptor V beta chain did not respond to SEA when cultured alone but exhibited STAT3 activation and IL-17 expression in co-cultures with SEA-responsive, non-malignant T cells.
The investigators found evidence to suggest the response is induced via IL-2Rg cytokines and a JAK3-dependent pathway in malignant T cells. The JAK3 inhibitor tofacitinib inhibited SEA-induced IL-17 production in co-cultures of malignant and non-malignant T cells.
Dr Oedum and his colleagues plan to continue their work investigating how bacteria might affect the balance between the immune defense mechanism and the disease in patients with CTCL.
In the long-term, the investigators’ aim is to understand how bacteria and their toxins can worsen CTCL, knowledge that may be used to develop new targeted treatments.
As only some of the bacteria produce toxins, the team said it will also be important to develop methods to determine which patients may benefit from treatment with antibiotics.
New research indicates that toxins in Staphylococcus bacteria help malignant cells gain control over healthy cells in patients with cutaneous T-cell lymphoma (CTCL).
Investigators found that staphylococcal enterotoxin-A (SEA) induces STAT3 activation and IL-17 expression in malignant T cells via engagement of non-malignant CD4 T cells.
As STAT3 activation has been implicated in CTCL pathogenesis, the discovery suggests bacterial toxins play a key role in activating an oncogenic pathway in CTCL.
“We have gained important insight into the processes that activate cancer cells and make them grow,” said Niels Oedum, MD, of the University of Copenhagen in Denmark.
“[CTCL] patients’ frequent bacterial infections might not be a mere side effect of the disease. On the contrary, toxins in the bacteria actually ‘benefit’ cancer cells. Our next step is examining whether combatting infections can slow down the growth of cancer cells and thus stop the disease.”
Dr Oedum and his colleagues described their research in Blood.
The investigators knew that, in CTCL, CD4 T cells become malignant and turn parasitic on the rest of the immune system. In addition to using healthy cells to do their work for them, the malignant cells slowly destroy the skin’s immune defense mechanism.
The team’s new discoveries indicate that bacterial toxins in some patients enable malignant cells to send off signals that obstruct and change the immune defense mechanism, which would otherwise fight the malignant cells. What was believed to be an overly active immune defense mechanism could, in other words, turn out to be a malignant infection brought on by bacteria, which only worsens the disease.
Dr Oedum and his colleagues found that SEA-positive bacteria isolatated from the skin of CTCL patients stimulated activation of STAT3 and upregulation of IL-17 in malignant and non-malignant T cells.
Malignant T cells expressing an SEA non-responsive T-cell receptor V beta chain did not respond to SEA when cultured alone but exhibited STAT3 activation and IL-17 expression in co-cultures with SEA-responsive, non-malignant T cells.
The investigators found evidence to suggest the response is induced via IL-2Rg cytokines and a JAK3-dependent pathway in malignant T cells. The JAK3 inhibitor tofacitinib inhibited SEA-induced IL-17 production in co-cultures of malignant and non-malignant T cells.
Dr Oedum and his colleagues plan to continue their work investigating how bacteria might affect the balance between the immune defense mechanism and the disease in patients with CTCL.
In the long-term, the investigators’ aim is to understand how bacteria and their toxins can worsen CTCL, knowledge that may be used to develop new targeted treatments.
As only some of the bacteria produce toxins, the team said it will also be important to develop methods to determine which patients may benefit from treatment with antibiotics.