resemble“wounds that do not heal”(Dvorak 1986, 2015; Schäfer and Werner
2008), which means that, in cancer, normal repair mechanisms are triggered but
generally without reaching the“resolution phase”(which, in the physiological
context, is indispensable to terminate the reparative process (Gurtner et al.
2008)). Furthermore, the tumor itself can be a major source of perturbation of
the local context: it can influence the immune system through a variety of
cytokines and can also increase inflammation and wounding, modify blood
vessels, reshape the extracellular matrix, or exert a mechanical pressure, among
many other possibilities. This is often described as the“hijacking”or“co-
option”by the tumor of physiological pathways and of the tissue microenvir-
onment (Kitano 2004a; Greaves 2007; Lean and Plutynski 2016). Despite its
importance, one must keep in mind that such co-option is only one of the many
ways in which the local context can become abnormal and favor the contribu-
tion of immune processes to cancer progression.
In all these contexts, immune-mediated decohesion results from the abnormal
realization of normal processes, and this can help explain why tumors largely
resemble organs (Egeblad et al. 2010) and are the products of classic develop-
mental (da Costa 2001; Radisky et al. 2001; Huang et al. 2009) and reparative
pathways (Bissell and Radisky 2001) realized in an abnormal context. There is no
doubt that the outcome is pathological (the promotion of a cancerous tumor,
including in some cases metastatic spread), but the immune system, in many of
these circumstances, does not strictly speaking“dysfunction”;itjustdoeswhatit
always does (maintaining the local environment, repairing in case of wound, etc.).
If the view presented here is correct, then a much richer picture emerges
about how the immune system influences cancer and, ultimately, of potential
therapeutic opportunities as well. Indeed, the immune system influences cancer
through different processes (elimination, containment, maintenance, repair, and
so on), via many actors (not only lymphocytes, but also macrophages, neutro-
phils, and various cytokines), at several different levels (within the tumor, but
also around the tumor, in the whole tissue, and at a systemic level in the
organism), and at all temporal stages of cancer progression (initiation, neoplas-
tic progression, and metastasis). Additionally, the influence of the immune
system on the cancerous tumor can be negative (the immune system prevents
cancer progression) or positive (the immune system promotes cancer progres-
sion). All this suggests a whole series of new opportunities for investigating
immunotherapies, which could, at least in principle, target these different
processes, actors, levels, and temporal stages. Current immunotherapies (parti-
cularly immune checkpoint inhibitors and CAR-Tcells (Joyce and Fearon 2015;
June and Sadelain 2018)) focus on lymphocytes in terms of actors and on
elimination and maintenance and rupture of chronicity in terms of processes,
42 Elements in the Philosophy of Biology