# NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions

## TL;DR

This paper reviews how NKG2D CAR-T cells could improve immunotherapy for solid tumors by overcoming the immunosuppressive tumor environment.

## Contribution

The paper provides a comprehensive review of recent innovations and challenges in NKG2D CAR-T cell therapy for solid tumors.

## Key findings

- NKG2D CAR-T cells target stress-induced ligands broadly expressed on tumor cells.
- Innovations in CAR architecture and signaling pathways have improved CAR-T cell function in solid tumors.
- Combination immunotherapy and armored CAR constructs show promise in overcoming TME barriers.

## Abstract

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in hematologic malignancies, but its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME) that hinders CAR-T cell trafficking and function. NKG2D CAR-T cells, which target stress-induced NKG2D ligands (NKG2DLs) broadly expressed on tumor cells, have shown promising potential in overcoming the immunosuppressive barriers of the solid TME. This review highlights recent advances in NKG2D CAR-T cell strategies for solid tumors, including innovations in CAR architecture, signaling pathway engineering, combination immunotherapy, and the development of armored CAR constructs. We further discuss the therapeutic potential, current challenges, and future directions of these approaches to inform the design of more effective and durable CAR-T cell therapies for solid tumors.