Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion

Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve “invasion” to tumors as the component. More and more tumor–nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients.