4.3 Immune–Cancer Interactions: Current Views
and Clinical Applications
Today, the evidence showing that the immune system plays a central role in
cancer development (either preventing or promoting cancer) is overwhelming
(Schreiber et al. 2011; Chen and Mellman 2017; Ribas and Wolchok 2018).
Many cellular and molecular immune components are involved in this process
of restriction or promotion of cancer. Additionally, these interventions of the
immune system can occur at different levels in or around the tumor (including
genes, cells, and the tumor microenvironment) and at every step of its progres-
sion, from initiation to neoplastic progression to metastasis. For example,
mouse models showed that tumor-associated macrophages promote angiogen-
esis and tissue remodeling, thereby favoring tumor growth. Clinical studies
show that extensive tumor-associated macrophage infiltration positively corre-
lates with cancer metastasis and poor clinical prognosis (Afik et al. 2016)
Investigations about the role of the immune system in cancer progression
have led to remarkable clinical applications. For example, several groups have
shown how, in a diversity of cancers, infiltration by certain immune components
had a better prognostic value than more traditional approaches (Galon et al.
2006). But most crucially, since the 2010s, the knowledge accumulated over
decades about immune-mediated control of cancerous tumors has turned into
specific clinical applications called“cancer immunotherapies,”which many
have described, rightly or wrongly, as“revolutionary”(Kelly 2018). After
extremely encouraging results obtained in melanoma and a few other cancer
types at the beginning of the 2010s (Hodi et al. 2010; Wolchok et al. 2013),
evidence in favor of the success of immunotherapies (increasingly, in fact,
a combination of immunotherapies) in several cancers has accumulated
(Ribas and Wolchok 2018). In a number of situations, the results have been
unprecedented and sometimes even spectacular, especially in cases of pre-
viously incurable cancers, raising much enthusiasm. Immunotherapies are
diverse but recently immune checkpoint inhibitors have been particularly
explored (Leach et al. 1996; Ribas and Wolchok 2018).
The most significant recognition of the work done in this area is undoubtedly the
2018 Nobel Prize in Physiology/Medicine awarded to James P. Allison and Tasuku
Honjo“for their discovery of cancer therapy by inhibition of negative immune
regulation,”which is centered on the blockade of immune checkpoints. This has
definitely convinced researchers working in all areas of cancer investigation and the
lay public that it is indispensable to pay attention to the role of the immune system in
cancer. It comes as no surprise that many newspapers have discussed these medical
advances, if perhaps sometimes hyperbolically (e.g., (Vonderheide 2018)).
Philosophy of Immunology 35