Radiotherapy-induced tumor physical microenvironment remodeling to overcome immunotherapy resistance

The clinical benefits of immunotherapy are proven in many cancers, but a significant number of patients do not respond well to immunotherapy. The tumor physical microenvironment (TpME) has recently been shown to affect the growth, metastasis and treatment of solid tumors. The tumor microenvironment (TME) has unique physical hallmarks: 1) unique tissue microarchitecture, 2) increased stiffness, 3) elevated solid stress, and 4) elevated interstitial fluid pressure (IFP), which contribute to tumor progression and immunotherapy resistance in a variety of ways. Radiotherapy, a traditional and powerful treatment, can remodel the matrix and blood flow associated with the tumor to improve the response rate of immune checkpoint inhibitors (ICIs) to a certain extent. Herein, we first review the recent research advances on the physical properties of the TME and then explain how TpME is involved in immunotherapy resistance. Finally, we discuss how radiotherapy can remodel TpME to overcome immunotherapy resistance.

Automated summary

The benefits of immunotherapy have been proven in many cancers, however, a significant number of patients do not respond well to this treatment. The tumor physical microenvironment (TpME) has been found to affect tumor growth, metastasis, and treatment. The unique physical hallmarks of the tumor microenvironment (TME) contribute to tumor progression and immunotherapy resistance. Radiotherapy, a traditional treatment, can remodel the TME and improve the response rate of immune checkpoint inhibitors (ICIs) to some extent.