Therapy-induced microenvironmental changes in cancer.

In the past decade, the focus of tumor biology research has been switching from the functional dissection of oncogenes and tumor suppressor genes to investigation of the cross-talk between tumor cells and their microenvironment. Tumorigenesis requires the organized assembly of cancer cells with non-malignant cells and non-cellular stroma, resembling an abnormal organogenesis. This process can be modulated by local cellular stress responses, such as senescence, ER stress and autophagy, and inflammatory and immunosuppressive cells and effector molecules within the tumor microenvironment (TME). Various cellular stress responses and cell death modalities are triggered in response to chemotherapies, radiotherapies, and targeted therapies (including immunotherapies). The exposure of immunostimulatory factors could (re)awaken anti-tumor immunity. Unexpectedly, the gut microbial flora is becoming recognized as an important external modulator of the TME. We will discuss in detail the TME changes that take place after certain cancer therapies, highlighting the importance of cellular stress responses, tumor-infiltrating immune cells, and microbiota-derived factors.