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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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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Cancer Stem Cells and Tumor Maintenance02:40

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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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CCL21 Programs Immune Activity in Tumor Microenvironment.

Sherven Sharma1,2,3, Pournima Kadam4, Steven Dubinett5,4,6

  • 1Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. SSharma@mednet.ucla.edu.

Advances in Experimental Medicine and Biology
|February 16, 2020
PubMed
Summary

Chemokine CCL21 enhances anti-tumor immunity by organizing immune cells within the tumor microenvironment (TME). Delivering CCL21 may restore immune activity, improving cancer immunotherapy effectiveness when combined with immune evasion pathway inhibition.

Keywords:
Activated T cellsAntigen-presenting cellsCCL21Dendritic cellsImmune activityImmune checkpoint blockadeImmune suppressionImmunotherapyProgrammed cell death protein 1 (PD-1)T cellsTumor microenvironment

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Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • The tumor microenvironment (TME) often exhibits suppressed immune activity, hindering effective anti-cancer responses.
  • Immune escape mechanisms are prevalent in the TME, facilitating tumor evasion of the immune system.
  • Chemokine CCL21 plays a role in immune cell trafficking and organization.

Purpose of the Study:

  • To investigate the role of CCL21 in modulating the tumor microenvironment for enhanced anti-cancer immunity.
  • To explore strategies for delivering CCL21 to reactivate suppressed immune responses in cancer patients.
  • To evaluate the potential of combining CCL21 delivery with inhibition of immune evasion pathways for improved cancer immunotherapy.

Main Methods:

  • Analysis of CCL21's function in promoting dendritic cell (DC) and T cell colocalization within the TME.
  • Assessment of ectopic lymph node-like structures formation induced by CCL21.
  • Correlation of these structures with cancer patient prognosis.
  • Exploration of novel delivery strategies for CCL21 in preclinical models.
  • Investigation of combined therapeutic approaches involving CCL21 and immune evasion pathway inhibitors.

Main Results:

  • CCL21 promotes the formation of ectopic lymph node-like structures in the TME by organizing dendritic cells and T cells.
  • These CCL21-induced structures correlate with improved cancer prognosis.
  • Reactivation of downregulated immune activity in the TME is achievable through CCL21 delivery.
  • Combined inhibition of dominant immune evasion pathways alongside CCL21 administration shows promise.

Conclusions:

  • CCL21 is a key mediator in enhancing anti-tumor immune activity within the TME.
  • Targeted delivery of CCL21 represents a promising strategy to overcome immune suppression in cancer.
  • Combination therapy involving CCL21 and blockade of immune evasion pathways holds potential for developing effective cancer immunotherapies.