Fundamental strides in the understanding of the molecular basis of tumor rejection were made in the last decade thanks to observational studies performed at relevant time points in human cancerous tissues. The following concepts emerged: immune surveillance against tumors is a likely occurrence. When cancer cells evolve to escape the ongoing immune defense, the neoplastic process reaches a clinically observable phase. By necessity, at this stage, escape mechanisms override anti-cancer mechanisms for tumors to be observable. When cancers become established, two molecular phenotypes can usually be observed: one is characterized by a tumor microenvironment infiltrated by immune cells bearing transcriptional signatures consistent with a status of partial activation. Although incapable of dramatically affecting tumor growth, immune infiltration bears a favorable prognostic and/or predictive connotation on the natural history of the disease or its responsiveness to therapy. In this chapter, we will discuss the significance of transcriptional signatures observed in pre-treatment biopsies as predictive of responsiveness to biological therapy. Moreover, we will discuss the transcriptional signatures observable during and after therapy documenting the switch from chronic to acute inflammation that leads to tumor rejection. We will further discuss how chemotherapy and viral oncolytic therapy, both believed to eliminate tumors exclusively through direct cytotoxicity may play an adjuvant role in stimulating this inflammatory switch. Finally, we will discuss how mechanisms leading to tumor rejection, largely overlap those associated with other aspects of immune-mediated tissue-specific destruction (TSD) such as allograft rejection, graft vs. host disease, acute clearance of pathogen and autoimmunity.
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