Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells.

Tumor resistance to therapy modalities is one of the major challenges to the eradication of cancer cells and complete treatment. Tumor includes a wide range of cancer and non-cancer cells that play key roles in the proliferation of cancer cells and suppression of anti-tumor immunity. For overcoming tumor resistance to therapy, it is important to have in-depth knowledge relating to intercellular communications within the tumor microenvironment (TME). TME includes various types of immune cells such as CD4 + T lymphocytes, cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, macrophages, and T regulatory cells (Tregs). Furthermore, some non-immune cells like cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs) are involved in the promotion of tumor growth. The interactions between these cells with cancer cells play a key role in tumor growth or inhibition. Resveratrol as a natural agent has shown the ability to modulate the immune system to potentiate anti-tumor immunity and also help to attenuate cancer cells and CSCs resistance. Thus, this review explains how resveratrol can modulate interactions within TME.