The Three Es of Cancer Immunoediting

Abstract

s Abstract After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models-together with compelling data from human patientsindicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoeditingelimination, equilibrium, and escape.

Tumour suppression by immune system through stochastic oscillations

“…Finally, as far as the phenomena of late recurrence of tumours are concerned, since they did not appear in our stochastic simulations, we think that they may have their main root in the phenomenon of immunoediting (Dunn et al 2004, d'Onofrio 2007) and we intend to study them, following the approach used in (d 'Onofrio 2007), by allowing, in the stochastic model, a slow decrease of some key parameters.…”

“…The presence of a very small equilibrium state that is not detectable might seem to be a sub-optimal outcome, so that one may consider it as practically equivalent to tumour suppression. However, it must be remembered that, as we mentioned in the introduction, the Volterrian interaction between tumour cells and the immune system is also evolutionary: tumour cells evolve their ability to evade the control (Dunn et al 2004, d'Onofrio 2007) and, as a consequence, no microscopic steady state may be considered permanent and safe for the patient (d 'Onofrio 2007).…”

“…Only in recent years has the study of cancer immunobiology accumulated a sufficient amount of evidence to show that tumours may be suppressed by immune system effectors. This has been made possible by the application of new molecular techniques and by performing a large number of epidemiological studies (Dunn et al 2004).…”

“…On the one hand, the presence of a small colony of tumour cells may result in metastases. On the other hand, over a long period of time, a significant fraction of the mean human life span, according to (Dunn et al 2004), the neoplasm may develop multiple strategies to circumvent the action of the immune system (Whiteside 2002, Pardoll 2003, Dunn et al 2004, Vicari et al 2002. This, in the long term, may allow it to evade immune surveillance and to re-commence growing to its carrying capacity.…”

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

“…The interaction of transformed cells with the immune system substantially influences whether the tumor cells are eliminated or progress to a life-threatening malignancy [26]. Evasion from this so-called immunosurveillance may occur due to selection of nonimmunogenic tumor cell subsets (also termed immunoselection or immunoediting) or by more or less active suppression of the immune response (also termed immunosubversion) [27].…”