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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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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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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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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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γδ T Cells in Tumor Microenvironment.

Caroline Imbert1,2, Daniel Olive3,4

  • 1Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity and Cancer, Institut Paoli Calmettes, Aix Marseille Université, Marseille, France.

Advances in Experimental Medicine and Biology
|October 29, 2020
PubMed
Summary

Gamma delta (γδ) T cells show potent anti-tumor activity but can be hindered by the tumor microenvironment. Enhancing Vγ9Vδ2 T-cell therapies by combining them with systemic approaches may improve cancer treatment efficacy.

Keywords:
ActivationBiomarkersButyrophilinCytokinesCytotoxicityDifferentiationImmunityImmunotherapyLymphocytesMicroenvironmentPhosphoantigensPlasticityRecruitmentTumorγδ T cells

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Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Gamma delta (γδ) T cells possess both innate and adaptive immune capabilities, exhibiting significant cytotoxic and pro-inflammatory functions against various tumor cells.
  • These cells are frequently found within tumors (tumor-infiltrating lymphocytes) and can serve as prognostic markers, although their role varies by cancer type, sometimes correlating with poor prognosis in breast and colon cancers.
  • The tumor microenvironment critically influences γδ T-cell behavior, potentially directing them towards tumor-promoting or tumor-controlling phenotypes, thus impacting their therapeutic effectiveness.

Purpose of the Study:

  • To review the fundamental characteristics of γδ T cells and their involvement in the tumor microenvironment.
  • To analyze recent advancements in understanding γδ T-cell activation within tumors and the associated therapeutic challenges.
  • To discuss current and future perspectives for γδ T-cell-based cancer immunotherapies.

Main Methods:

  • Review of existing scientific literature on γδ T cells, tumor microenvironment interactions, and immunotherapeutic strategies.
  • Analysis of the activation mechanisms of Vγ9Vδ2 T cells, including their reliance on butyrophilin 3A (BTN3A) expression.
  • Examination of ex vivo and in vivo therapeutic approaches utilizing γδ T cells.

Main Results:

  • γδ T cells are crucial in anti-tumor immunity, with Vγ9Vδ2 T cells being a major subset activated by phosphoantigens via BTN3A.
  • The tumor microenvironment can modulate BTN3A expression and γδ T-cell function, presenting challenges for immunotherapy.
  • Current therapeutic strategies involving Vγ9Vδ2 T cells, such as adoptive transfer and in vivo expansion, show promise but require optimization.

Conclusions:

  • γδ T cells, particularly Vγ9Vδ2 T cells, hold significant therapeutic potential against cancer due to their potent anti-tumor properties.
  • Overcoming the immunosuppressive effects of the tumor microenvironment and optimizing T-cell activation are key challenges for effective γδ T-cell immunotherapy.
  • Combining γδ T-cell-based therapies with systemic treatments to modulate the tumor microenvironment may enhance overall anti-tumor immune responses and improve patient outcomes.