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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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Tumor Immunotherapy01:27

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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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Cells of the Innate Immune Response01:28

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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
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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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Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
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Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56brightCD16- subset.

Irene Veneziani1, Claudia Alicata1, Andrea Pelosi1

  • 1Department of Immunology, Bambino Gesu Pediatric Hospital, Roma, Italy.

Journal for Immunotherapy of Cancer
|January 29, 2022
PubMed
Summary

Toll-like receptor 8 (TLR8) agonists activate natural killer (NK) cells, enhancing their anti-tumor functions. This finding suggests TLR8 as a promising target for cancer immunotherapy, particularly for ovarian carcinoma.

Keywords:
adjuvantsimmunologicimmunotherapykiller cellsnaturalreceptorstumor microenvironment

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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
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Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Toll-like receptors (TLRs) are crucial for innate immunity, recognizing pathogen-associated molecular patterns (PAMPs).
  • Natural killer (NK) cells express endosomal TLRs, responding to viral and bacterial nucleic acids.
  • Understanding NK cell activation via specific TLRs is vital for developing effective cancer immunotherapies.

Purpose of the Study:

  • To determine which endosomal TLRs directly mediate NK cell activation and function.
  • To identify the optimal TLR agonist for use as an adjuvant in cancer vaccines and immunotherapies.
  • To investigate the specific TLR pathway responsible for activating the CD56brightCD16- NK cell subset.

Main Methods:

  • Assessed endosomal TLR expression in NK cell subsets (CD56brightCD16- and CD56dimCD16+) using RT-qPCR and western blotting.
  • Evaluated NK cell activation markers, cytokine production, and cytotoxicity via flow cytometry and ELISA.
  • Analyzed NK cells from ovarian ascites of patients with metastatic ovarian carcinoma.

Main Results:

  • Endosomal TLR3, TLR7/8, and TLR9 were expressed on both NK cell subsets.
  • TLR7/8 (R848), TLR3 (Poly I:C), and TLR9 (ODN2395) ligands enhanced NK cell function with suboptimal cytokines.
  • R848 primarily activated CD56brightCD16- NK cells via TLR8, increasing proliferation, cytokine production, and cytotoxicity, an effect also observed in patient-derived NK cells.

Conclusions:

  • TLR8 activation is a key driver of NK cell-mediated anti-tumor responses.
  • Targeting TLR8 on NK cells presents a novel strategy for cancer immunotherapy.
  • These findings are particularly relevant for treating metastatic ovarian carcinoma.