Biophysical and mechanobiological considerations for T-cell-based immunotherapy

Area of Science:

• Oncology
• Immunology
• Biophysics
• Mechanobiology

Background:

• Cancer immunotherapies show promise but have limited response rates and severe side effects.
• Current immunotherapy development often neglects the crucial roles of biophysical and mechanobiological factors.
• The tumor microenvironment presents significant biophysical cues that influence both immune and tumor cells.

Purpose of the Study:

• To review the impact of biophysical and mechanobiological factors on cancer immunotherapy.
• To highlight the role of mechanosensing pathways (e.g., Piezo1, YAP/TAZ) in tumor-immune interactions.
• To explore how biophysical methods can improve engineered T-cell therapies.

Main Methods:

• Literature review focusing on immune biophysics and mechanobiology in cancer.
• Analysis of studies investigating mechanosensing in immune cells and tumor cells.
• Examination of biophysical techniques for enhancing T-cell manufacturing and function.

Main Results:

• Mechanosensing pathways critically influence tumor-immune cell interactions and immunotherapy effectiveness.
• Biophysical cues within the tumor microenvironment modulate treatment outcomes.
• Advanced biophysical methods offer improved control and specificity for engineered T-cell therapies.

Conclusions:

• Integrating biophysics and mechanobiology is essential for advancing cancer immunotherapy.
• Targeting mechanosensing mechanisms presents novel strategies for improving therapeutic efficacy.
• Biophysical approaches hold potential for optimizing chimeric antigen receptor (CAR) T-cell and anti-programmed cell death protein 1 (anti-PD-1) therapies.