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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The Tumor Microenvironment02:17

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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SIRT1 Inhibits T Cell Infiltration and Tertiary Lymphoid Structure Formation to Promote Radioimmunotherapy

Yunxing Shi1, Zong-Feng Wu2, Shaoru Liu2

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Microsatellite stable rectal cancer resists immunotherapy. Targeting SIRT1 with aspirin and radiotherapy overcomes this resistance by enhancing anti-tumor immunity and improving responses to immune checkpoint inhibitors.

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Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Microsatellite stable (MSS) rectal cancer is resistant to immunotherapy.
  • Radiotherapy combined with immune checkpoint inhibitors (ICIs) shows limited efficacy in many cold tumors.

Purpose of the Study:

  • To investigate mechanisms of radioimmunotherapy resistance in MSS rectal cancer.
  • To identify therapeutic targets to overcome resistance and improve treatment outcomes.

Main Methods:

  • Transcriptomic screening and in vivo experiments were performed.
  • Mechanistic studies explored the role of SIRT1 in regulating immune responses.
  • Combination therapy involving SIRT1 inhibitor and aspirin with radiotherapy was evaluated.

Main Results:

  • SIRT1 deacetylated DDX5, suppressing cGAS/STING pathway activation and T cell infiltration.
  • A positive feedback loop involving tryptophan, SIRT1, and SLC36A4 inhibited tertiary lymphoid structure formation.
  • Combination therapy converted ICI-unresponsive tumors into immunogenic tumors sensitive to ICI.

Conclusions:

  • SIRT1 is a key regulator of radioimmunotherapy resistance in MSS rectal cancer.
  • Targeting SIRT1 presents a promising strategy to enhance immunotherapy efficacy.
  • Combination of SIRT1 inhibitor and aspirin with radiotherapy offers a potential therapeutic approach.