Tumour microenvironment (TME) is a key determinant of tumour growth and
metastasis. TME could be very different for each type and location of tumour and TME may change constantly during tumour growth. Multiple counterparts in surrounding microenvironment including mesenchymal-, hematopoietic-originated cells as well as non-cellular components affect TME. Thus,
therapeutics that can disrupt the tumour-favouring microenvironment should be further explored for
cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of TME components has identified numerous
protein tyrosine kinases, while its corresponding inhibitors have demonstrated potent modulatory effect on TME. Recent works have demonstrated that beyond the direct action on
cancer cells,
tyrosine kinase inhibitors (TKIs) have been implicated in inactivation or normalization of dysregulated TME components leading to
cancer regression. Either through re-sensitizing the tumour cells or reversing the immunological tolerance microenvironment, the emergence of these TME modulatory mechanism of TKIs supports the combinatory use of TKIs with current
chemotherapy or
immunotherapy for
cancer therapy. Therefore, an appropriate understanding on TME modulation by TKIs may offer another mode of action of TKIs for
cancer treatment. This review highlights mode of
kinase activation or paracrine
ligand production from TME components and summarises the findings on the potential use of various TKIs on regulating TME components. At last, the combination use of current TKIs with
immunotherapy in the perspectives of efficacy and safety are discussed.