Cell Rep. Med.: Tumor-microenvironment-modulating microspheres to augment tumor-infiltrating lymphocyte therapy against solid tumors

Authors：

Mingkang Li^1,2, Shen Yan¹, Xiaoying Yan², Ziwei Nie¹, Haihan Wang², Qiaofeng Li², Haoqi Liu³, Wenzhuo Yu², Shuai Zhang², Yanbin Liu², Hong Chen¹*, Winston Duo Wu¹*, Yu Chao²*, Zhuang Liu²*

Institutions：

¹The College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu, 215123, China

²Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, China

³College of Nano Science and Technology, Soochow University, Suzhou, Jiangsu, 215213, China

Abstract：

Tumor-infiltrating lymphocyte (TIL) therapy is a T cell therapy approved for treating solid tumors. However, the dense extracellular matrix (ECM) and immunosuppressive tumor microenvironment (TME) result in limited numbers and activities of initially harvested TILs, further leading to time-consuming preparation processes and suboptimal treatment efficacy. Herein, we develop alginate-based hydrogel microspheres co-loaded with hyaluronidase (HAase) and chemokine CXCL9. With released HAase to degrade the extracellular matrix and CXCL9 to recruit lymphocyte infiltration, such microspheres after intratumoral injection allow effective TME modulation, leading to greatly enhanced TIL numbers in tumors. TILs collected from those pre-treated tumors exhibit not only accelerated ex vivo expansion but also markedly improved activities and anti-exhaustion capacities. Those TILs after re-infusion could significantly inhibit tumor growths and metastases in different tumor models. Our work demonstrates that modulating TME before tumor collection may be an effective and clinically practical approach to boost current TIL therapies.

IF：

10.6

Link：

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00211-9