Engineering tumor stromal mechanics for improved T cell therapy

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 4; p. 130095
• Main Authors: Ying, Linxuan, Yazdani, Mahsa, Koya, Richard, Zhao, Ruogang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: antigens; Cell- and Tissue-Based Therapy; fibrosis; Humans; immunotherapy; Immunotherapy, Adoptive; mechanics; neoplasms; Neoplasms - pathology; Neoplasms - therapy; Receptors, Antigen, T-Cell - genetics; T-lymphocytes; Tumor Microenvironment
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2022.130095

Adoptive cellular therapies (ACT), including the engineered T cell receptor (TCR) therapy and chimeric antigen receptor (CAR) T Cell Therapy, are currently at the forefront of cancer immunotherapy. However, their efficacy for the treatment of solid tumors has not been confirmed. The fibrotic stroma surrounding the solid tumor has been suggested as the main barrier in the disarmament and suppression of the engineered T cells. In this review, we will discuss the recent findings on the mechanism of T cell suppression by the tumor stroma with a special emphasis on the effect of stromal mechanics. We will also discuss the engineering approaches used to dissect the mechanism of the T cell suppression by the stromal mechanical factors. Finally, we will provide a future outlook on the strategies to improve the efficacy of T cell therapy through altering the tumor stromal fibrosis. •The fibrotic stroma surrounding the solid tumor serve as a main barrier in suppressing engineered T cells.•The tumor stroma is characterized by its unique structure, composition and mechanical properties.•Engineered tumor stroma models have been used to examine the mechanism of T cell suppression.•Integration of multiple stromal microenvironmental factors in future models is needed.