Tumor Microenvironment Interactions in Cancer Progression

The tumor microenvironment (TME) comprises a complex and dynamic network of malignant cells, stromal elements and non-cellular components that collectively drive cancer progression. Reciprocal signalling between cancer cells and surrounding fibroblasts, immune infiltrates and endothelial cells promotes proliferation, invasion and metastasis. Extracellular matrix remodelling alters tissue stiffness and intercellular communication, while metabolic crosstalk supports rapid growth and therapy resistance. Immune cells within the TME may be co-opted to secrete cytokines that suppress antitumor responses or to present antigens, shaping immunosurveillance. Angiogenesis and lymphangiogenesis, orchestrated by vascular cells and pericytes, ensure nutrient delivery and facilitate dissemination. Insights into these interactions have underscored the global significance of targeting both cellular and non-cellular components of the TME to improve therapeutic outcomes and overcome resistance.

Research from Nature Portfolio

Recent consensus research has established a comprehensive framework for categorising cancer-associated fibroblasts (CAFs) according to their developmental origins, phenotypic markers and functional roles within the TME. This work delineates distinct protumorigenic and antitumorigenic fibroblast subsets, elucidating the signalling pathways that regulate matrix deposition, immune modulation and reciprocal crosstalk with malignant cells. By identifying key molecular circuits that drive fibroblast activation, the approach offers precise strategies to target tumor-promoting CAFs while preserving or harnessing antitumor subpopulations, thus informing the development of stromal-directed therapies in cancer.

Tumor Microenvironment Interactions in Cancer Progression publication trend

The graph below shows the total number of articles in tumor microenvironment interactions in cancer progression across all publications each year (not limited to Nature Index journals).

Technical terms

Cancer-associated fibroblasts (CAFs): stromal cells within the TME that secrete matrix components and signalling molecules to influence tumor progression.

Extracellular matrix (ECM): a network of fibrous proteins and glycoproteins that provides structural support and biochemical cues to cells.

Immunosuppressive microenvironment: local milieu where immune surveillance is hindered by suppressive cells and soluble factors, enabling tumor evasion.

Angiogenesis: the formation of new blood vessels from pre-existing vasculature, a process essential for tumor growth and metastatic spread.

References

1. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Communication and Signaling (2020).
2. A framework for advancing our understanding of cancer-associated fibroblasts. Nature Reviews Cancer (2020).
3. Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials. Molecular Cancer (2023).
4. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Molecular Cancer (2021).