New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape

Abstract

The principles of cancer immunoediting have set the foundations for understanding the dual host-protective and tumor sculpting actions of immunity on cancer and establishing the basis for novel individualized cancer immunotherapies. During cancer immunoediting, the host immune system shapes tumor fate in three phases through the activation of innate and adaptive immune mechanisms. In the first phase, Elimination, transformed cells are destroyed by a competent immune system. Sporadic tumor cells that manage to survive immune destruction may then enter an Equilibrium phase where editing occurs. The Escape phase represents the third and final phase of the process, where immunologically sculpted tumors begin to grow progressively, become clinically apparent and establish an immunosuppressive tumor microenvironment. This review focuses on important recent developments that have enhanced our understanding of each phase of the cancer immunoediting process, summarizes the discovery of new predictive and prognostic biomarkers and discusses development of novel and objectively effective cancer immunotherapies.

Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune‐deficient mice

“…T cells and IFN‐γ mediate cancer immune surveillance (Mittal et al ., 2014). eRapa mediated remarkably potent lifespan (Fig.…”

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

“…The latter mediate the interactions of tumor cells with host's immune system. 6,82 In contrast, limited information is available about the impact of immune selection on HLA class II antigen expression by tumor cells. We are aware of only one example suggesting that immune selection facilitates the outgrowth of HLA class II antigen-negative tumor cells: MSI-H CRCs are characterized by a pronounced antitumoral immune response, which is triggered by a high amount of mutation-induced neoantigens.…”

“…Alterations of HLA class I APM and their significance in malignant tumors have been recently reviewed by various groups and we refer the interested reader to these reviews. [3][4][5][6][7][8] In contrast, HLA class II antigens expressed by malignant cells of solid tumors have been characterized only to a limited extent, although the aberrant expression of HLA class II antigens by melanoma cells was first described more than 30 y ago. 9 Growing evidence indicates that HLA class II antigen expression by tumor cells has a significant impact on their immunogenicity.…”

Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma

“…21 A genomic approach to TAA identification should hasten steps in the development of cancer immunotherapies, i.e., in the evaluation of the advancement of immune-editing, selection of highly immunogenic tumors for personalized therapy, and identification of TAAs that drive addictive oncogenic pathways needed for cancer cell survival. 16 TAAs as targets for vaccines Four criteria have to be met before use of a TAA as a potential target for a vaccine.…”

“…17 The balance between activation and inhibition is maintained by immuno-editing. Evidence for immunosurveillance, which relies on T-cell response to tumorassociated antigens (TAA), 16 comes from rare cases of spontaneous complete responses observed in the placebo arm of a phase III trial. 18 The blood and tumor microenvironment of these cases harbored TAA-specific T-cells; the tumors were highly infiltrated by TAA-specific effector memory CD8 T-cells and CD4 T-cells.…”