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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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Related Experiment Video

Updated: May 10, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Acquired resistance to immunotherapy in solid tumors.

Perrine Verdys1, Astrid Z Johansen1, Anurag Gupta2

  • 1National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.

Trends in Molecular Medicine
|April 24, 2025
PubMed
Summary

Acquired resistance to immunotherapy (ARI) hinders long-term success in solid tumors for many patients. Understanding complex tumor-intrinsic and extrinsic mechanisms is crucial for developing effective interventions against ARI.

Keywords:
ICIacquired resistanceimmunotherapiessolid tumors

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Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Acquired resistance to immunotherapy (ARI) is a significant clinical challenge in solid tumors, affecting up to 65% of initially responsive patients.
  • Standardized clinical definitions for ARI are still under development, highlighting the complexity of this phenomenon.

Purpose of the Study:

  • To review recent advancements in understanding the multifaceted mechanisms underlying acquired resistance to immunotherapy in solid tumors.
  • To emphasize the importance of comprehending ARI development for the creation of preventative strategies and effective treatments.

Main Methods:

  • This review synthesizes current research on tumor-intrinsic and extrinsic factors contributing to ARI.
  • It examines mechanisms including antigen processing defects, interferon-gamma (IFNγ) insensitivity, T cell exclusion, metabolic reprogramming, and the role of the tumor microenvironment.

Main Results:

  • ARI involves complex tumor-intrinsic mechanisms like antigen loss and IFNγ insensitivity.
  • Extrinsic factors such as immunosuppressive cells, extracellular matrix remodeling, and microbiota dysbiosis also play critical roles.
  • Tumor-mediated T cell exclusion and metabolic reprogramming are identified as key contributors.

Conclusions:

  • A comprehensive understanding of ARI's diverse mechanisms is essential for clinical management.
  • Integrating novel therapeutic strategies with translational research using well-characterized samples is vital for overcoming ARI and achieving durable patient benefits.