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Related Concept Videos

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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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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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Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.

Paul A Beavis1, Clare Y Slaney1, Michael H Kershaw2

  • 1Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville 3010, Australia.

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Summary

Adoptive cellular therapy (ACT) shows promise for more cancers. Combining ACT with novel strategies may overcome the immunosuppressive tumor microenvironment, expanding its use beyond blood cancers.

Keywords:
Adoptive cellular therapyCancerChimeric antigen receptorImmunosuppressionImmunotherapy

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Cancer immunotherapy is rapidly advancing, targeting more cancer types with new therapeutics.
  • Adoptive cellular therapy (ACT), including chimeric antigen receptor (CAR) T cells, is primarily effective in hematological malignancies and some immunogenic solid tumors.
  • Current ACT efficacy in solid tumors is limited, potentially due to the immunosuppressive tumor microenvironment.

Purpose of the Study:

  • To review the potential of novel combination strategies for adoptive cellular therapy (ACT) in treating a broader range of cancers.
  • To outline the clinical relevance of targeting the immunosuppressive tumor microenvironment for enhancing ACT efficacy.

Main Methods:

  • Review of current clinical trials and research on adoptive cellular therapy (ACT) for solid tumors.
  • Analysis of strategies aimed at overcoming tumor microenvironment-mediated immunosuppression.
  • Synthesis of findings on combination approaches involving ACT.

Main Results:

  • ACT, including tumor-infiltrating lymphocytes (TIL) and engineered T cells (CAR/TCR), has shown limited efficacy in many solid cancers.
  • The immunosuppressive tumor microenvironment is a significant barrier to ACT effectiveness.
  • Novel combination strategies targeting tumor-induced immunosuppression are emerging as promising approaches.

Conclusions:

  • Combination therapies hold significant potential to expand the application of ACT to a wider spectrum of solid cancers.
  • Overcoming the immunosuppressive tumor microenvironment is crucial for improving ACT outcomes.
  • Further research and clinical trials are needed to validate these combination strategies.