Collection |

The tumour microenvironment

The tumour mass consists not only of a heterogeneous population of cancer cells but also a variety of resident and infiltrating host cells, secreted factors and extracellular matrix proteins, collectively known as the tumour microenvironment. Tumour progression is profoundly influenced by interactions of cancer cells with their environment that ultimately determine whether the primary tumour is eradicated, metastasizes or establishes dormant micrometastases. The tumour microenvironment can also shape therapeutic responses and resistance, justifying the recent impetus to target components of the tumour microenvironment, which is best exemplified by the success of immune checkpoint inhibitors in the clinic.

This Collection of the most recently published articles from Nature Reviews Cancer showcases the diverse aspects of tumour microenvironment research, and we hope it will be a valuable resource to research scientists, clinicians and students interested in this field.

Reviews

This Review discusses nutrient scavenging, a process by which cancer cells use macromolecules from their environment to fuel cell metabolism and growth even when nutrients are limiting.

Review Article | | Nature Reviews Cancer

Although the aggressive underlying biology of inflammatory breast cancer (IBC) remains largely undefined, the tumour microenvironment (TME) has emerged as a key contributor. This Review discusses intrinsic characteristics of IBC, extrinsic features of the TME and intrinsic–extrinsic communication.

Review Article | | Nature Reviews Cancer

The adenosinergic pathway is a major immunosuppressive mechanism in the tumour microenvironment. In this Review, Vijayanet al. discuss how targeting components involved in the generation and downstream signalling of extracellular adenosine represents an attractive novel cancer therapy.

Review Article | | Nature Reviews Cancer

This Review by Corbet and Feron summarizes recent data showing that tumour acidosis influences cancer metabolism and contributes to cancer progression; it also highlights advances in therapeutic modalities aimed at either inhibiting or exploiting tumour acidification.

Review Article | | Nature Reviews Cancer

This Review discusses the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

Review Article | | Nature Reviews Cancer

The human microbiota influences a whole range of physiological functions. In this Review, Roy and Trinchieri discuss our current understanding of how the gut microbiota modulates responses to cancer therapy as well as mediating susceptibility to toxic side effects.

Review Article | | Nature Reviews Cancer

Perspectives

This Opinion proposes that temporal variations in intratumoural blood flow are the result of eco-evolutionary dynamics. It describes adaptive strategies to stochastically varying environments that may strongly affect observed cancer phenotypes and clinical outcomes including formation of metastases and response to treatment.

Perspective | | Nature Reviews Cancer

This Opinion discusses the role of the primary cilium as a platform for pathways implicated in cancer and how changes in the ciliation of cells in the tumour microenvironment can affect cancer progression.

Perspective | | Nature Reviews Cancer

In this Timeline article, Maman and Witz describe how much progress has been made in understanding how the tumour microenvironment influences tumour progression since its initial description, highlighting the controversies in the field and the potential of targeting components of the microenvironment for cancer therapy.

Perspective | | Nature Reviews Cancer

The abscopal effect, which is the regression of metastatic cancer at distant sites during radiotherapy, is somewhat rare but can be promoted by immunotherapy. This Opinion article describes emerging concepts and limitations of using a combination of radiotherapy and immunotherapy to boost the abscopal effect.

Opinion | | Nature Reviews Cancer

Emerging data indicate that exercise modulates cancer biology and disease outcomes; however, the molecular mechanisms are poorly established. In this Opinion article, the authors speculate on how exercise might reprogramme the tumour microenvironment to influence cancer hallmarks.

Opinion | | Nature Reviews Cancer

Research highlights

Priego et al. show that a subpopulation of reactive astrocytes expressing signal transducer and activator of transcription 3 (STAT3) is crucial for the development of brain metastases and report positive initial clinical data that inhibiting STAT3 can reduce metastasis.

Research Highlight | | Nature Reviews Cancer

Tumour-associated neutrophils can inhibit the proliferation of pro-tumoural interleukin-17 (IL-17)+ γδ T cells via production of reactive oxygen species.

Research Highlight | | Nature Reviews Cancer

Han et al. have identified a new tumour-induced immune cell population in the spleen that can promote tumour growth through production of the neurotrophic factor artemin.

Research Highlight | | Nature Reviews Cancer

Using clinical tissue specimens and mouse models of breast cancer, Incio et al. show that obesity promotes the upregulation of interleukin-6 and fibroblast growth factor 2 in the tumour microenvironment, which confer resistance to anti-vascular endothelial growth factor therapy.

Research Highlight | | Nature Reviews Cancer

In a new study, researchers show that basal-like breast cancer can be converted into the luminal subtype by inhibiting platelet-derived growth factor (PDGF)-CC signalling in the tumour microenvironment, thereby potentially broadening treatment options for oestrogen receptor-negative breast cancer patients.

Research Highlight | | Nature Reviews Cancer

Wang, C., Wang, J. et al. show that local injection of a hydrogel scaffold degraded by reactive oxygen species in the tumour microenvironment releases chemotherapy and an immune checkpoint inhibitor with kinetics that increase antitumour responses.

Research Highlight | | Nature Reviews Cancer

Activation of TGFβ signalling in invasive margins of metastatic tumours can contribute to T cell exclusion and reduced immune checkpoint therapy response. Inhibition of TGFβ in non-responders can potentially help to improve outcomes in these patients.

Research Highlight | | Nature Reviews Cancer

Three recent papers have shed light on how the common oncogenic drivers MYC and RAS can induce an immunosuppressive tumour microenvironment.

Research Highlight | | Nature Reviews Cancer

Reactive oxygen species derived from inflammatory myeloid cells is sufficient to induce mutagenesis in intestinal epithelial cells, independently of cytokines, to promote tumour initiation and progression.

Research Highlight | | Nature Reviews Cancer

The gut microbiome can modulate the clinical response to anti-programmed cell death protein 1 (PD1) immunotherapy in patients with solid tumours.

Research Highlight | | Nature Reviews Cancer