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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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Loss of Tumor Suppressor Gene Functions01:12

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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Structures of Solids02:22

Structures of Solids

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Solids in which the atoms, ions, or molecules are arranged in a definite repeating pattern are known as crystalline solids. Metals and ionic compounds typically form ordered, crystalline solids. A crystalline solid has a precise melting temperature because each atom or molecule of the same type is held in place with the same forces or energy. Amorphous solids or non-crystalline solids (or, sometimes, glasses) which lack an ordered internal structure and are randomly arranged. Substances that...
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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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Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Tumor Progression02:07

Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Related Experiment Video

Updated: Jan 29, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
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Three-Dimensional Tumor Spheroids Reveal B7-H3 CAR T Cell Infiltration Dynamics and Microenvironment-Induced

Feng Chen1,2, Ke Ning1, Yuanyuan Xie1

  • 1Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China.

Cells
|January 28, 2026
PubMed
Summary

This study introduces a 3D tumor spheroid model to overcome limitations in evaluating chimeric antigen receptor (CAR) T cell therapy for solid tumors. The platform effectively models the tumor microenvironment (TME) and assesses CAR T cell efficacy against cancer spheroids.

Keywords:
3D tumor spheroidsB7-H3CAR T cellsT cell infiltrationimmunotherapytumor microenvironment

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Last Updated: Jan 29, 2026

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Microfluidic Device for Recreating a Tumor Microenvironment in Vitro
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Microfluidic Device for Recreating a Tumor Microenvironment in Vitro

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Chimeric antigen receptor (CAR) T cell therapy shows promise in hematologic cancers but faces challenges in solid tumors due to the tumor microenvironment (TME).
  • Existing 2D cell culture models fail to accurately represent the complex TME, limiting the assessment of CAR T cell therapy efficacy in solid tumors.

Purpose of the Study:

  • To validate a 3D tumor spheroid platform for evaluating CAR T cell therapy in solid tumors.
  • To assess the impact of the TME on CAR T cell function and efficacy using a novel 3D model.

Main Methods:

  • Developed a 3D tumor spheroid model using an agarose microwell system to generate uniform B7-H3-positive spheroids from solid tumor cell lines.
  • Analyzed TME-relevant immune modulation (B7-H3, MHC I/II, APM) in 3D spheroids via flow cytometry.
  • Co-cultured spheroids with B7-H3 CAR T cells to evaluate cytotoxicity, tumor viability, and CAR T cell activation, exhaustion, and cytokine production.

Main Results:

  • The 3D platform successfully generated B7-H3-positive spheroids from prostate (DU 145) and breast (SUM159) cancer cell lines.
  • 3D spheroids exhibited TME-like immune evasion characteristics, downregulating MHC-I and antigen processing machinery (APM) while upregulating MHC-II and calreticulin.
  • CAR T cells effectively infiltrated spheroids, demonstrating cytotoxicity, structural disruption, and enhanced activation, exhaustion, and effector function, including increased IFN-γ and TNF-α production.

Conclusions:

  • The validated 3D tumor spheroid platform effectively recapitulates critical TME constraints relevant to CAR T cell therapy.
  • This 3D model provides a feasible and cost-effective preclinical tool for assessing CAR T cell therapies in solid tumors, outperforming traditional 2D assays.