NO. 63

CIMR Wednesday Lecture Series

Time:

Wednesday, Mar. 26 2025, 4:00 p.m.

Location:

Yifu Lecture Hall, North Basic Research Building 

Host：

Shao-Cong Sun (孙少聪)

Chinese Institutes for Medical Research, Beijing

Speaker：

Bo Huang (黄波)

Institute of Basic Medical Sciences

Chinese Academy of Medical Sciences and Peking Union Medical College

TITLE：

Power of softness in mechano-onco-immunology

ABSTRACT:

Stiffness is a fundamental mechanical trait of cells, which is described as the resistance to deformation. Softness is the opposite of stiffness, consistent with cellular deformation. Cell stiffness is decided by cytoskeletons, mainly by microfilaments, having little relationship to microtubules or intermediate filaments. Adapting mechanobiology principles, we found that soft 3D fibrin gel culture system can effectively amplify stem cell-like tumor cells. Conventional surface markers are not stable; in contrast, mechanical softness is stable and can act as an ideal marker of tumor-repopulating cells or cancer stem cells. This softness can be used by tumor-repopulating cells to dampen perforin pore formation, thus evading T cell killing; however, drug-packaging microparticles use TRCs’ softness to enter TRCs and activate the lysosomal pathway to deliver drug molecules into the nucleus, inducing soft tumor cell death. Perforin pore formation is unidirectional to avoid T cell autolysis. This is because effector T cells are also very soft. Three dimension fibrin gels are suitable to amplify not only TRCs but also stem-like CAR T cells, achieving CAR T treatment of solid tumors.

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