The tumour microenvironment

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.

In this Review, Di Virgilio et al. describe how extracellular ATP and P2 purinergic signalling can shape the tumour microenvironment to both promote and restrain tumour progression and outline the opportunities to harness nucleotide receptor signalling as an anticancer strategy.

In this Review, Hamidi and Ivaska discuss the contribution of integrins to the different steps of cancer progression, highlighting some of the recently identified unconventional roles of integrins and novel opportunities to target integrin signalling.

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.

This Review describes tumour cell-intrinsic oncogenic pathways implicated in tumour immune evasion and highlights the potential for targeting these pathways to overcome resistance to immunotherapy in various cancer types.

This Review by Dewhirst and Secomb describes the current understanding of drug transport to tumour cells and the progress that has been made in developing methods to enhance drug delivery.

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.

This Review by Mitchellet al. summarizes how engineering and the physical sciences have advanced oncology by highlighting four important areas: the physical microenvironment of the tumour, drug delivery, cellular and molecular imaging, and microfluidics and microfabrication.

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.

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.

Insights into the effects of targeted therapies, conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical responses in patients.

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.

This Review summarizes the natural progression of pre-metastatic niche formation and evolution, highlighting recent advances and future hurdles.

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.

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.

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.

In this Opinion article, Donnemet al. outline the evidence for non-angiogenic tumours, which use pre-existing blood vessels to support tumour growth, and discuss the studies that are beginning to define their unique biology.

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.

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.

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.

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

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.

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.

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.

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.

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.

A subset of cancer-associated firboblasts, defined by the presence of the cell surface markers CD10 and GPR77, promotes tumour formation and chemoresistance by providing a niche for cancer stem cells.

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

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.

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