Focused radiation may help turn on the immune system

Non-ASPS articles which could be relevant.
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D.ap
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Focused radiation may help turn on the immune system

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Debbie
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Re: Focused radiation may help turn on the immune system

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“Much of the buzz over doctors’ ability to harness the power of the immune system to fight cancer has focused on targeted treatments—drugs designed to zero in on specific properties of cancer cells, disrupting their signals and exposing them to an immune attack. Now, researchers are discovering that these and other immunotherapy drugs may be even more powerful when combined with conventional therapies like chemotherapy. “We’re finding ways to make the immune system stronger through drug combinations,” says Christian Hyde, MD, Radiation Oncologist at our hospital near Atlanta. But the tactic has limitations: Mixing too many drugs together often leads to significant side effects, such as autoimmune diseases, that may make the combinations impractical. One combination, though, is showing exciting, and promising, results, though they are still considered rare. Researchers are finding that combining immunotherapy with focused radiation treatments delivered directly to the tumor sometimes shrinks not just the targeted tumor, but cancers located in areas of the body that were not radiated.”
Debbie
D.ap
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Re: Focused radiation may help turn on the immune system

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My main purpose for posting in the medical topic, reserved for ASPS, is to receive data and or info that folks have received , pertaining to positive results and or data to possibly bring good results , specific to ASPS.

Had a friend ask these questions -

1 does ASPS respond to radiation with inflammation
2 are there effective inhibitors for treg production

Thanks in advance
Debbie
Debbie
D.ap
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Regulatory T cells: a potential target in cancer immunotherapy

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#2-

Abstract
Cancer immunotherapy involving blockade of immune checkpoint molecules, such as CTLA-4 and PD-1, has shown remarkable clinical success across several types of malignancies. However, a fraction of patients experience disease progression after treatment; thus, exploring resistant mechanisms for immune checkpoint inhibitors and improving their treatment outcome with additional modalities are of great importance. CD4+ regulatory T (Treg ) cells characterized by expression of the master regulatory transcription factor FOXP3 are a highly immune-suppressive subset of CD4+ T cells that maintain immune homeostasis. Several preclinical and clinical studies suggest that Treg cells hamper immune surveillance against cancer in healthy individuals, prevent the development of effective antitumor immunity in tumor-bearing patients, and promote tumor progression. Therefore, targeting Treg cells should be crucial to improving the treatment outcomes of cancer immunotherapy. Several clinical studies directly or indirectly targeting Treg cells in combination with immune checkpoint inhibitors are ongoing or being planned. Understanding the characteristics and roles of Treg cells in cancer settings could make disease-specific Treg -targeted therapy more efficacious and reduce the incidence of immune-related adverse effects mediated by Treg cell inhibition.

https://www.ncbi.nlm.nih.gov/m/pubmed/29566262/
Last edited by D.ap on Wed Dec 11, 2019 9:04 pm, edited 1 time in total.
Debbie
D.ap
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Regulatory T cells in cancer immunotherapy

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Abstract
FOXP3-expressing regulatory T (Treg) cells, which suppress aberrant immune response against self-antigens, also suppress anti-tumor immune response. Infiltration of a large number of Treg cells into tumor tissues is often associated with poor prognosis. There is accumulating evidence that the removal of Treg cells is able to evoke and enhance anti-tumor immune response. However, systemic depletion of Treg cells may concurrently elicit deleterious autoimmunity. One strategy for evoking effective tumor immunity without autoimmunity is to specifically target terminally differentiated effector Treg cells rather than all FOXP3+ T cells, because effector Treg cells are the predominant cell type in tumor tissues. Various cell surface molecules, including chemokine receptors such as CCR4, that are specifically expressed by effector Treg cells can be the candidates for depleting effector Treg cells by specific cell-depleting monoclonal antibodies. In addition, other immunological characteristics of effector Treg cells, such as their high expression of CTLA-4, active proliferation, and apoptosis-prone tendency, can be exploited to control specifically their functions. For example, anti-CTLA-4 antibody may kill effector Treg cells or attenuate their suppressive activity. It is hoped that combination of Treg-cell targeting (e.g., by reducing Treg cells or attenuating their suppressive activity in tumor tissues) with the activation of tumor-specific effector T cells (e.g., by cancer vaccine or immune checkpoint blockade) will make the current cancer immunotherapy more effective.


https://www.nature.com/articles/cr2016151
Debbie
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Re: Focused radiation may help turn on the immune system

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Introduction
A number of studies have shown that self-antigen or tumor antigen-specific CD4+ and CD8+ T cells are present in healthy individuals1,2,3,4. How such self- or tumor-reactive T cells are controlled in healthy or tumor-bearing individuals remains to be determined. Mechanisms for the maintenance of immunological self-tolerance (i.e., unresponsiveness to self-antigens) not only prevent autoimmunity but also hamper effective tumor immunity because many tumor antigens recognized by autologous lymphocytes are normal self-antigens or quasi-self-antigens with genetic mutations. This is one reason why it is difficult to elicit strong tumor immunity in cancer-bearing patients by cancer vaccine alone5. It also suggests that effective tumor immunity can be evoked by breaching a certain mechanism(s) of immunological self-tolerance systemically or locally in tumor tissues.

Among the various mechanisms of immunological self-tolerance, immune suppression by endogenous Foxp3+CD25+CD4+ Treg cells is essential and indispensable as illustrated by spontaneous autoimmune disease development when Treg cells are rendered deficient. For example, mutations of the gene encoding the Treg-specific transcription factor Foxp3 impair Treg cell development and cause a fatal multi-organ autoimmune disease called immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome6. Depletion of Foxp3+CD25+CD4+ Treg cells by a variety of methods is also able to cause similar autoimmune diseases in otherwise normal rodents7.

On the other hand, it is now well substantiated that a large number of Treg cells infiltrate into tumor tissues of various cancers and their abundant presence is often associated with poor clinical prognosis. Experimentally, the role of Treg cells in tumor immunity was first demonstrated by an attempt to determine a common basis between tumor immunity and autoimmunity8. Removal of Treg cells using cell-depleting anti-CD25 antibody, either by in vivo antibody administration to mice or transfer of cell suspension depleted in vitro of CD25+ Treg cells into histocompatible T-cell-deficient mice, effectively eradicated a variety of inoculated syngeneic tumors8,9. The mice showed an increase of tumor-infiltrating CD8+ T cells with strong tumor-specific killing activity, and upon re-challenge with the same tumor cells, exhibited more rapid rejection than the primary rejection, indicating the establishment of tumor-specific immunity8,10. These studies have thus demonstrated that the removal of Treg cells is able to evoke effective anti-tumor immunity by abrogating immunological unresponsiveness to syngeneic tumors, albeit it may also cause autoimmunity, especially if Treg cells are depleted systemically.

In this review, we discuss molecular basis of Treg functions and their behavior in tumor tissues, and strategies to target Treg cells, in particular their subsets, in order to evoke effective anti-tumor immunity in humans, without eliciting deleterious autoimmunity.
Debbie
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