Chemokines regulate the infiltration of different immune cell subsets into tumours and, as such, these molecules affect tumour immunity and influence therapeutic outcomes in patients.
Chemokines also target tumour cells and stromal cells, and they regulate tumour angiogenesis, stemness, proliferation and survival.
Chemokine expression is regulated intrinsically by epigenetic and genetic pathways, and also extrinsically by hypoxia, metabolic cues and the microbiota.
Targeting chemokine networks may alter tumour biological and immunological phenotypes, and increase antitumour immune responses.
Therapies that target chemokines could synergize with existing cancer therapies, including current immunotherapies.
The tumour microenvironment is the primary location in which tumour cells and the host immune system interact. Different immune cell subsets are recruited into the tumour microenvironment via interactions between chemokines and chemokine receptors, and these populations have distinct effects on tumour progression and therapeutic outcomes. In this Review, we focus on the main chemokines that are found in the human tumour microenvironment; we elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology, and we consider how they affect cancer immunity and tumorigenesis. We also discuss the potential of targeting chemokine networks, in combination with other immunotherapies, for the treatment of cancer.
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The authors thank their former and current collaborators and trainees for their intellectual input and hard work. The work described in this Review was supported by grants from the US National Institutes of Health (NIH; F31CA189440) and the Herman and Dorothy Miller Award for Innovative Immunology Research to N.N.; NIH grants CA193136, CA190176, CA171306, CA152470, CA099985, CA156685, CA123088, CA133620, CA092562, CA100227 and CA211016 to W.Z.; and NIH grant R35 CA129765 to M.S.W. The Review focuses mainly on the human cancer immune microenvironment and cancer patient-oriented studies. Owing to the plethora of literature related to the topic described in this Review, the writing of a complete and extensive article is extremely challenging. The authors apologize in advance for any inadvertent omissions.
W.Z. is a consultant to NGM Bio and Lycera, and has received research grants from Medimmune, NGM Bio and Lycera. M.S.W. is a co-founder of, and holds equity in, Oncomed Pharmaceuticals, and serves as a consultant for MedImmune and Verastem. N.N. declares no competing interests.
- Cancer stem-like cell
A cell that can self-propagate, is less-differentiated and can give rise to other tumour cells. These properties enable these cells to be potentially key players in tumour initiation, metastasis, and treatment resistance and/or cancer relapse.
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Nagarsheth, N., Wicha, M. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 17, 559–572 (2017). https://doi.org/10.1038/nri.2017.49
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