Beyond the tumour microenvironment

Abstract

In contrast to the once dominant tumour-centric view of cancer, increasing attention is now being paid to the tumour microenvironment (TME), generally understood as the elements spatially located in the vicinity of the tumour. Thinking in terms of TME has proven extremely useful, in particular because it has helped identify and comprehend the role of nongenetic and noncell-intrinsic factors in cancer development. Yet some current approaches have led to a TME-centric view, which is no less problematic than the former tumour-centric vision of cancer, insofar as it tends to overlook the role of components located beyond the TME, in the 'tumour organismal environment' (TOE). In this minireview, we highlight the explanatory and therapeutic shortcomings of the TME-centric view and insist on the crucial importance of the TOE in cancer progression.

Keywords: immune system; microbiome; nervous system; tumour microenvironment; tumour organismal environment.

Figure 1

Elements located far from the tumour microenvironment can influence cancer progression. Investigations on cancer growth and dissemination have tended to focus on the causal influence of elements located within the tumour itself or in its immediate vicinity, that is, in the tumour microenvironment (TME). Nevertheless, elements that do not belong to the TME can sometimes have a major impact on cancer progression, including the immune system, the nervous system, and the microbiome. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

The role of the TOE in the therapeutic response. (a) Recruitment of pro‐angiogenic immune cells by the TOE can promote resistance to VEGF inhibitors; (b) The TOE can play an essential role in the efficacy of some therapies such as cancer vaccines that lead to clonal selection of tumour‐specific T cells in secondary lymphoid structures, away from the tumour site itself; (c) The microbiota, localised within the TOE, may also modulate the efficacy of different therapies such as immunotherapies; (d) Therapies can also exhibit adverse effects on the TOE: for instance, while killing cancer cells, chemotherapies can negatively impact the haematopoietic system, leading to a more pro‐tumorigenic TME. Abbreviations: T, tumour; TME, tumour microenvironment; TOE, tumour organismal environment. The tumour is represented in yellow and the classical TME‐centric view is in green, TME‐centrism overlooks the involvement of the TOE (in blue) in the response to therapies (in red).