Cancer Self-Defense: An Immune Stealth

Abstract

The hurdles in realizing successful cancer immunotherapy stem from the fact that cancer patients are either refractory to immune response and/or develop resistance. Here, we propose that these phenomena are due, in part, to the deployment/secretion of a "decoy flare," for example, anomalous cancer-associated antigens by the tumor cells. The cancer secretome, which resembles the parent cell make-up, is composed of soluble macromolecules (proteins, glycans, lipids, DNAs, RNAs, etc.) and insoluble vesicles (exosomes), thus hindering cancer detection/recognition by immunotherapeutic agents, resulting in a "cancer-stealth" effect. Immunotherapy, or any treatment that relies on antigens' expression/function, could be improved by the understanding of the properties of the cancer secretome, as its clinical evaluation may change the therapeutic landscape. Cancer Res; 77(20); 5441-4. ©2017 AACR.

Figure 1.

The complexity of cancer secretory elements and immune interventions is illustrated. Cancer cell releases secretory factors composed of cancer-derived soluble antigens (green) and exosomes (red). Endogenous/exogenous antibodies, that is, patient-derived AAbs (blue) and therapeutic AAbs (red) are blocked due to the cancer secretory stealth effect. Killer cells, for example, natural killer cells, T lymphocytes, tumor-associated macrophages, neutrophils, and dendritic cells (light blue) may also join the reactions. On the basis of correlation analyses between AAbs and tumor-derived factors, the tumor-derived factors may be classified into three groups: class I, not inducible; class II, not susceptible; class III, positive susceptibility. The cancer cell image was purchased from Shutterstock.