Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

Abstract

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.

Keywords: T lymphocytes; extracellular matrix; immune escape; targeted therapy; tumor microenvironment.

Figure 1

The ECM in the tumor microenvironment. The tumor microenvironment mainly consists of tumor cells, immune cells, stromal cells, and ECM. The ECM is composed of proteins, glycans, and proteoglycans, and is an important part of the tumor microenvironment.

Figure 2

ECM receptors and associated signaling pathways. Common receptors in T-cell-ECM interactions include integrins, DDR, LAIR1, CD44, and SDC, through which changes in the extracellular matrix regulate multiple intracellular signaling pathways.

Figure 3

Interactions between T cells and ECM. ECM density and hardness increase in the tumor microenvironment, which inhibits T cell activation and migration. T cells induce ECM degradation and remodeling by secreting chemokines and cytokines, and then regulate anti-tumor immune response.

Figure 4

Targeting ECM for tumor therapy. Several possible strategies for targeting ECM for tumor treatment include targeting the ECM components, ECM-related receptor blocked, CAR-T cell therapy, drug delivery, and Bioprinting.