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Related Concept Videos

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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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Reprogramming Postablation Tumor Immune Microenvironment with Dual-Function Nanotherapeutic Immunomodulator for

Bing Wang1, Zhicheng Yan2,3, Yuhan Shen1

  • 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Peking University, Beijing 100142, China.

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Radiofrequency ablation (RFA) for liver tumors can cause immune suppression. A new nanotherapy reverses this suppression and boosts anti-tumor immunity, effectively reducing tumor recurrence.

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STING pathway activationimmunosuppressionmyeloid-derived suppressor cellsradiofrequency ablationtumor recurrence

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Area of Science:

  • Oncology
  • Immunology
  • Nanomedicine

Background:

  • Radiofrequency ablation (RFA) is a key treatment for liver tumors, but tumor recurrence post-ablation is a significant clinical issue.
  • RFA can induce immunosuppression, mainly through myeloid-derived suppressor cells (MDSCs), hindering the host immune system's ability to fight residual cancer.
  • Harnessing RFA's potential to stimulate anti-tumor immunity requires overcoming this immunosuppressive environment.

Purpose of the Study:

  • To develop a nanotherapeutic strategy that simultaneously reverses RFA-induced immunosuppression and enhances anti-tumor immune responses.
  • To investigate the efficacy of co-delivering a STING agonist and an MDSC-differentiating agent to modulate the systemic immune landscape post-ablation.

Main Methods:

  • Engineered nanoparticles (cA@NPs) co-encapsulating 2",3"-cyclic guanosine adenosine monophosphate (cGAMP), a STING agonist, and all-trans retinoic acid (ATRA), an MDSC-differentiating agent.
  • Evaluated the nanotherapeutic strategy in residual tumor models to assess its impact on immunosuppression and anti-tumor immunity.
  • Conducted comprehensive preclinical evaluations to determine the capacity of cA@NPs to suppress micrometastasis, distant tumors, and orthotopic lesions.

Main Results:

  • Reversing MDSC-driven immunosuppression post-ablation is crucial for effective anti-tumor immunity.
  • The engineered cA@NPs successfully reversed post-RFA immunosuppression and activated the STING pathway for immune priming.
  • Preclinical studies demonstrated that cA@NPs significantly suppressed tumor growth, including micrometastasis and distant lesions, by remodeling the immune microenvironment.

Conclusions:

  • The developed nanotherapeutic immunomodulatory strategy effectively bridges localized thermal ablation with systemic immune potentiation.
  • This approach offers a promising avenue for clinical translation to combat liver tumor recurrence by synergizing RFA with nanotherapy.
  • The findings provide a mechanistic basis for using nanomedicine to enhance the anti-tumor efficacy of RFA and address a critical clinical challenge.