Modulating tumor physical microenvironment for fueling CAR-T cell therapy

Area of Science:

• Immunology
• Biomedical Engineering
• Oncology

Background:

• CAR T-cell therapy is highly effective against blood cancers but faces challenges in solid tumors.
• Solid tumors present physical barriers including heterogeneous antigen expression, an immunosuppressive tumor microenvironment (TME), and immune evasion.
• The physical tumor microenvironment significantly impacts CAR T-cell therapy efficacy.

Purpose of the Study:

• To review the critical roles of physical cues in the solid tumor microenvironment on CAR T-cell immune responses.
• To highlight strategies that exploit these physical features to enhance CAR T-cell therapy for solid tumors.
• To provide future perspectives on developing novel CAR T-cell therapies for solid tumors.

Main Methods:

• Literature review focusing on the impact of physical tumor microenvironment on CAR T-cell therapy.
• Analysis of four key physical cues: solid stress, interstitial fluid pressure, stiffness, and microarchitecture.
• Correlation of physical cues with state-of-the-art technologies for enhancing CAR T-cell potency.

Main Results:

• Physical cues like solid stress, interstitial fluid pressure, stiffness, and microarchitecture critically regulate CAR T-cell function in solid tumors.
• These physical factors impede CAR T-cell infiltration, transportation, and antitumor activity.
• Exploiting these physical features offers novel strategies to improve CAR T-cell therapy outcomes.

Conclusions:

• Understanding and targeting the physical tumor microenvironment is crucial for advancing CAR T-cell therapy in solid tumors.
• New strategies leveraging physical cues can enhance the therapeutic efficacy of CAR T-cells.
• Future research should focus on integrating physical microenvironment modulation into CAR T-cell treatment paradigms for solid tumors.