Cancer immunoediting hypothesis: history, clinical implications and controversies

Abstract

The main function of the immune system is to protect against infectious pathogens and to ensure tissue homeostasis. The latter function includes preventing autoimmune reactions, tolerizing cells to nonpathogenic environmental microorganisms, and eliminating apoptotic/damaged, transformed, or neoplastic cells. The process of carcinogenesis and tumor development and the role of the immune system in inhibiting progression of cancer have been the subject of intense research since the end of the 20^th century and resulted in formulation of the cancer immunoediting hypothesis. The hypothesis postulates three steps in oncogenesis: 1) elimination - corresponding to immunosurveillance, 2) equilibrium in which the growth of transformed or neoplastic cells is efficiently controlled by immune effector mechanisms, and 3) escape in which cancer progresses due to an ineffective antitumor response. In parallel, a new field of science - immune-oncology - has arisen. Attempts are also being made to quantify intra-tumoral and peritumoral T cell infiltrations and to define optimal immunological parameters for prognostic/predictive purposes in several types of cancer. The knowledge of relationships between the tumor and the immune system has been and is practically exploited therapeutically in the clinic to treat cancer. Immunotherapy is a standard or supplementary treatment in various types of cancer.

Keywords: cancer immunoediting; immune contexture; tumor immunology.

Fig. 1

Relationships between transformed/tumor cells and the protective antitumor response – cancer immunoediting hypothesis. The process of cancer immunoediting consists of three stages: elimination, equilibrium, and escape. In the elimination phase, transformed cells are killed by antitumor effector mechanisms. Some of these cells can survive and enter the equilibrium phase in which variants of cancer cells are generated that can avoid an immune attack. In the escape phase, the tumor grows progressively due to promotion of local immunosuppression which allows the antitumor response to be evaded (see details in the text) (modified from [30])