Cancers are not just masses of malignant cells but complex ‘rogue’ organs, to which many other cells are recruited and can be corrupted by the transformed cells. Interactions between malignant and non-transformed cells create the tumor microenvironment (TME). The non-malignant cells of the TME

The tumor microenvironment at a glance

The development of tumor-specific T cell tolerance is largely responsible for tumor escape. Accumulation of myeloid-derived suppressor cells (MDSCs) in animal tumor models as well as in cancer patients is involved in tumor-associated T cell tolerance. In recent years, it has become increasingly evident that MDSCs bring about antigen-specific T cell tolerance by various mechanisms, which is the focus of this chapter.

https://cancerimmunolres.aacrjournals.org/content/canimm/5/1/3.full.pdf

Myeloid-Derived Suppressor Cells

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets.

/pdf/neutrophils-in-cancer-neutral-no-more-2eb9s218qg.pdf

Neutrophils in cancer: neutral no more

It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

/pdf/pre-metastatic-niches-organ-specific-homes-for-metastases-2ckqpo28s3.pdf

Pre-metastatic niches: organ-specific homes for metastases

The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells?

The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.

https://cancerres.aacrjournals.org/content/canres/70/15/6139.full.pdf

Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung

We appreciate the letter by Bosiljcic and colleagues raising questions about our studies published in Cancer Research , in which we showed that Gr-1+CD11b+ cells alter the premetastatic lung in an inflammatory and proliferative environment, diminish immune protection, and induce aberrant vasculature

https://cancerres.aacrjournals.org/content/canres/early/2011/07/08/0008-5472.CAN-11-0688.full.pdf

Jerome W. Gray

Papers

Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung

Myeloid Suppressor Cells Regulate the Lung Environment—Response