Thermoelectric catalysis overcomes tumour “marginalization” of cytotoxic T-lymphocytes to boost immune checkpoint blockade therapy

Abstract

Although immune checkpoint blockade (ICB) therapy enhances the tumour recognition of cytotoxic T lymphocytes (CTLs), the limited infiltration of CTLs into the centre of solid tumours significantly restricts the effect of ICB therapy. Herein, we showed that increased tumour interstitial fluid pressure (TIFP) is a critical factor in the tumour “marginalization” of CTLs. Additionally, we utilized a spatiotemporally controllable thermoelectric catalytic nanodrug (BF@M) to decompose water from the tumour interstitial fluid into oxygen, effectively reducing the TIFP and leading to enhanced infiltration of CTLs from the periphery to the interior of the solid tumour. The results revealed that BF@M significantly increased the intratumor infiltration of CTLs in three different tumour-bearing mouse models, with a maximum increase of 18.1 times. Overall, this study highlighted the intrinsic relationship between TIFP and CTLs infiltration and the mechanism underlying the effect of the TIFP, successfully addressing the tumour “marginalization” of CTLs to enhance ICB therapy.