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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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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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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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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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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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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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CCL22-specific T Cells: Modulating the immunosuppressive tumor microenvironment.

Evelina Martinenaite1, Shamaila Munir Ahmad1, Morten Hansen1

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Oncoimmunology
|December 22, 2016
PubMed
Summary
This summary is machine-generated.

Activating T cells targeting CCL22 (chemokine C-C motif ligand 22) can kill cancer cells. This approach reduces regulatory T cells (Tregs) in tumors, potentially boosting anticancer immunity.

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AntigenCCL22T cellsTregsanti-Tregs

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Tumor cells and macrophages produce CCL22, attracting regulatory T cells (Tregs) that suppress anticancer immunity.
  • Targeting CCL22-expressing cells offers a potential strategy to enhance anti-tumor responses.

Purpose of the Study:

  • To investigate targeting CCL22-expressing cells by activating specific T cells.
  • To identify and utilize a CCL22-derived peptide epitope for T cell activation.

Main Methods:

  • Analyzed CCL22 signal sequence to identify an HLA-A2-restricted T cell epitope.
  • Expanded CCL22-specific T cells from peripheral blood mononuclear cells (PBMCs) in vitro.
  • Assessed T cell recognition and lysis of CCL22-expressing cancer cells and leukemia cells.
  • Used Enzyme-Linked ImmunoSPOT (ELISPOT) assay and tetramer enrichment/depletion experiments.

Main Results:

  • CCL22-specific T cells recognized and killed CCL22-expressing cancer cells and acute monocytic leukemia cells.
  • Spontaneous T cell responses against the CCL22 epitope were detected in cancer patients and healthy donors.
  • Activation of CCL22-specific T cells reduced CCL22 levels in the microenvironment.

Conclusions:

  • Activating CCL22-specific T cells can directly target cancer cells and tumor-associated macrophages.
  • This strategy may reduce Treg infiltration into tumors, thereby augmenting anticancer immunity.
  • CCL22-specific T cells represent a promising therapeutic approach for cancer treatment.