西南交通大学发表最新Cell子刊论文

Core Viewpoint - The article discusses the development of a hydrogel-fiber composite device (HFCD) aimed at enhancing the efficacy of immune checkpoint blockade (ICB) therapy for recurrent glioblastoma (GBM) by activating cytotoxic T lymphocytes (CTL) in the postoperative tumor microenvironment (pTME) [2][3][5]. Group 1: Background on Glioblastoma and ICB Therapy - Glioblastoma (GBM) is the most common and aggressive brain tumor, accounting for approximately 57% of all gliomas, with a recurrence rate exceeding 90% due to its invasive nature [5]. - The postoperative tumor microenvironment (pTME) is characterized by immune suppression, including CTL exhaustion and infiltration of immunosuppressive cells, which reduces the clinical benefits of ICB therapy [5][6]. - There is a need to reshape the immune landscape within the pTME to enhance the response and durability of ICB therapy against GBM recurrence [5][6]. Group 2: Development of HFCD - The HFCD is designed to locally activate CTLs and modulate the acidic pTME, creating a favorable niche for CTLs [3][8]. - The device releases chemokine CXCL10 and PD-L1 inhibitors in a timed manner, enhancing CTL infiltration and maintaining their cytotoxic function [3][8]. - In an in situ GBM resection model, HFCD treatment achieved a 40% rate of complete recurrence inhibition and significantly extended the median survival to 49 days [9][10]. Group 3: Mechanism of Action - HFCD consists of quaternized chitosan hydrogel and electrospun fibers, which neutralize the acidic pTME and release CXCL10 to recruit CTLs [8]. - The sustained release of PD-L1 inhibitors from the PLGA matrix maintains PD-L1 blockade, enhancing CTL recognition and cytotoxic activity against residual GBM cells [8][10]. - This strategy alleviates immune suppression in the GBM pTME and enhances the protective effect of ICB against GBM recurrence [8][10].