2026/01/19 by Yan Zhang, Huihui Sun, Lianfeng Zhao +5
paper · doi:10.1111/imm.70094
crossref issued 2026/01/19 · crossref published 2026/01/19 · crossref published-online 2026/01/19 · crossref created 2026/01/19 · crossref deposited 2026/04/15 · crossref published-print 2026/05/01 · crossref indexed 2026/07/29
ABSTRACT Chimeric antigen receptor T (CAR‐T) cell therapy has revolutionised the treatment of hematologic malignancies, achieving durable and robust responses. However, the application of CAR‐T cells in solid tumours remains limited by a complex network of barriers, most notably poor tumour infiltration. The key obstacles include mismatch between chemokines and receptors, abnormal tumour vasculature, immunosuppressive cellular populations (such as myeloid‐derived suppressor cells, tumour‐associated macrophages and regulatory T cells), dense network of cancer‐associated fibroblasts and extracellular matrix, T cell dysfunction and exhaustion, metabolic limitations within the tumour microenvironment, tumour heterogeneity and transport limitations related to tumour location. By integrating mechanistic insights with innovative bioengineering and combination approaches, this review systematically elaborates on the factors that limit the infiltration of CAR‐T cells and emphasises transformation strategies for improving the efficacy, durability and invasiveness of treating solid tumours.