The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tumors have only focused on the development and progression of a tumor from a mechanistic standpoint; few studies have examined whether the changes in the TME can also affect tumor growth and drug resistance. Recently, emerging evidence have raised more concerns regarding the role of TME in the development of drug resistance. In the present review, it was discussed how the suppressive TME adapts to drug resistance characterized by the cooperation of immune cells, cytokines, immunomodulators, stromal cells and extracellular matrix. Furthermore, it was reviewed how these immunological or metabolic changes alter immuno‑surveillance and thus facilitate tumor drug resistance. In addition, potential targets present in the TME for developing novel therapeutic strategies to improve individualized therapy for cancer treatment were revealed.
Keywords: cancer‑associated fibroblasts; drug resistance; extracellular matrix; tumor immune microenvironment; tumor‑associated macrophages.