or suppress the immune response) and have a higherfitness in the immuno-
competent host (a process similar to the selection of more resistant pathogens).
Therefore, Robert Schreiber and colleagues proposed to use the term immu-
noediting instead of the traditional notion of immunosurveillance, reflecting the
fact that the immune system not only monitors tumors but also shapes them,
with both beneficial and detrimental consequences for the host (Dunn et al.
2002; Schreiber et al. 2011). Immunoediting is a more encompassing and more
accurate concept, especially because it emphasizes the diachronic character of
cancer development.
The concept of immunoediting is well-suited to describe the dual host-
protecting and tumor-sculpting actions of the immune system. According to
its proponents, immunoediting encompasses three different though largely
overlapping processes, referred to as the“3e’s”(see Figure 4.1):“elimina-
tion”(which corresponds to the classic idea of immunological surveillance,
that is, the destruction of tumor cells by the immune system),“equili-
brium”(the immune system iteratively selects and/or promotes the genera-
tion of tumor cell variants with increasing capacities to survive immune
destruction), and“escape”(the immunologically sculpted tumor expands
beyond control in the host) (Dunn et al. 2002). In 2007, a landmark study
by Schreiber’sgroupconfirmed the existence of the equilibrium phase
(Koebel et al. 2007).
The processes by which the immune system can have a tumor-promoting
effect go well beyond immunoediting and are actually quite diverse. In
particular, tumor-associated macrophages (TAMs) can sometimes be tumor-
suppressive, but in a majority of cases they favor tumor initiation, progres-
sion, and metastasis (Mantovani et al. 1992; Wynn et al. 2013). Indeed,
macrophages can sustain the chronic inflammation that often plays a role in
tumor initiation and promotion (Mantovani et al. 2008), skew adaptive
immune responses, and facilitate cell growth, angiogenesis (Murdoch
et al. 2008), matrix deposition, tissue remodeling (Mantovani et al. 2013;
Afik et al. 2016), and metastasis (Qian and Pollard 2010). The exact effects
of macrophages located in or around the tumor also depend on the tem-
poral sequence of events: tumor-preventing macrophages can switch to
a tumor-promoting role depending on the cues they receive from the
tumor microenvironment (Wynn et al. 2013). So-called myeloid-derived
suppressor cells (MDSCs) contribute to cancer and metastasis (Kumar et al.
2016 ), and tumor-associated neutrophils (Fridlender et al. 2009)aswellas
regulatory T cells (Tanaka and Sakaguchi 2017) also, in many circum-
stances, can promote cancer.
Philosophy of Immunology 33