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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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Antigens Involved in Adaptive Immunity01:26

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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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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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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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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Beyond HLA-Ia: A multidimensional framework for Neoantigen immunotherapy.

Liurui Ding1, Chenjing Guo1, Yehao Qin1

  • 1Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China.

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|April 30, 2026
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Summary

This review proposes a genotype-agnostic immunotherapy framework for malignant gliomas. Strategies like HLA-E, γδ T cells, AI, and BBB delivery aim to overcome immune escape and improve treatment outcomes.

Keywords:
Glioma immunotherapyHLA-EImmune escapeNon-classical HLA-Ibγδ T cells

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Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Malignant gliomas, including glioblastoma (GBM), exhibit aggressive progression, high recurrence, and poor prognoses.
  • Current therapies offer limited survival benefits for glioma patients.
  • Existing neoantigen immunotherapies face significant hurdles in gliomas, such as HLA-Ia downregulation, tumor heterogeneity, immunosuppressive microenvironment, and the blood-brain barrier (BBB).

Purpose of the Study:

  • To review recent advances in overcoming immunotherapy barriers in gliomas.
  • To propose a multidimensional framework for developing broadly applicable neoantigen immunotherapies.
  • To establish a genotype-agnostic foundation for glioma treatment.

Main Methods:

  • Exploring HLA-E as an alternative antigen-presentation platform.
  • Investigating γδ T cells to bypass classical HLA-Ia dependence.
  • Utilizing artificial intelligence (AI) for neoantigen prioritization and optimization.
  • Examining emerging BBB-penetrating delivery technologies.

Main Results:

  • The proposed strategies aim to decouple neoantigen targeting from individual HLA restrictions.
  • This framework facilitates the development of "genotype-agnostic" immunotherapies.
  • The integrated approach enhances translational feasibility for glioma treatments.

Conclusions:

  • A multidimensional framework integrating novel strategies can overcome key barriers to effective glioma immunotherapy.
  • This approach holds promise for developing broadly applicable, off-the-shelf neoantigen immunotherapies.
  • The proposed framework offers new directions for overcoming immune escape in malignant gliomas.