The changing role of natural killer cells in cancer metastasis

Chan, Isaac S.; Ewald, Andrew J.

doi:10.1172/jci143762

Cited by 53 publications

(40 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously in ex vivo and mouse models, we observed that NK cells can be ’reprogrammed’ after exposure to malignant mammary epithelial cells to promote tumor outgrowth (10, 11). To determine the human significance of this finding, we first generated a signature of mouse reprogrammed NK (rNK) cells based on an experiment (10) comparing the transcriptomes of healthy NK cells to tumor-exposed NK cells that we found to be tumor promoting (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response

Saunders

Knútsdóttir

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

We present an integrated single-cell RNA-seq resource of the breast tumor microenvironment consisting of 236,363 cells from 119 biopsy samples across 8 publicly available datasets. In this computational study, we first leverage this novel resource to define cancer epithelial cell heterogeneity based on two clinically relevant markers and define six new and distinct subsets of natural killer cells. We then illustrate how cancer epithelial cell heterogeneity impacts immune cell interactions. We develop T cell InteractPrint, which considers how cancer epithelial cell heterogeneity shifts the predicted strength of T cell interactions. We use InteractPrint to predict response to immune checkpoint inhibition (ICI) in two clinical trials testing immunotherapy in patients with breast cancer. T cell InteractPrint was predictive in both trials (AUC=0.81 and 0.84), versus PD-L1 expression (AUC=0.54 and 0.72). This result provides an alternative predictive biomarker to PD-L1 to select patients who should receive ICI.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Their cytotoxic activity is regulated by a series of functionally activating and inactivating receptors. After tumor exposure, the balance of activating and inactivating receptors can change, and they can lose their cytotoxic activity, proliferative capacities, or even become tumor-promoting (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response

Saunders

Knútsdóttir

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…MDSC-CTL interactions are important given the primary function of intratumoral MDSCs is suppression of CTLs (1, 6, 15, 16). MDSC-NK interactions are also important (20–22, 24, 25), and NK cells are increasingly being studied as an immune population specifically affected by tumor cells to promote metastasis (46, 47). A schematic diagram of the model is provided in Figure 1.…”

Section: Methodsmentioning

confidence: 99%

Myeloid-derived suppressor cell dynamics control outcomes in the metastatic niche

Kreger

Torres

MacLean

2022

Preprint

View full text Add to dashboard Cite

Myeloid-derived suppressor cells (MDSCs) play a prominent and rising role in the tumor microenvironment. An understanding of the tumor-MDSC interactions that influence disease progression is critical, and currently lacking. To address this, we developed a mathematical model of metastatic growth and progression in immune-rich tumor microenvironments. We model the tumor-immune dynamics with stochastic delay differential equations, and study the impact of delays in MDSC activation/recruitment on tumor growth outcomes. We find when the circulating level of MDSCs is low, the MDSC delay has a pronounced impact on the probability of new metastatic establishment: blocking MDSC recruitment can reduce the probability of metastasis by as much as 50%. We also quantify the extent to which decreasing the immunosuppressive capability of the MDSCs impacts the probability that a new metastasis will persist or grow. In order to quantify patient-specific MDSC dynamics under different conditions we fit individual tumors treated with immune checkpoint inhibitors to the tumor-MDSC model via Bayesian parameter inference. We reveal that control of the inhibition rate of natural killer cells by MDSCs has a larger influence on tumor outcomes than controlling the tumor growth rate directly. Posterior classification of tumor outcomes demonstrates that incorporating knowledge of the MDSC responses improves predictive accuracy from 63% to 82%. Our results illustrate the importance of MDSC dynamics in the tumor microenvironment and predict interventions that may shift environments towards a less immune-suppressed state. We argue that there is a pressing need to more often consider MDSCs in analyses of tumor microenvironments.

show abstract

Section: Nk Cellsmentioning

confidence: 99%

“…NK cells have been found altered in their phenotype and functions in diverse solid and hematological cancers [136,137]. In solid cancers, hypofunctional NK cells have been found both at tumor tissue and peripheral levels [136][137][138][139]. As shared features of cell anergy in cancers, NK cells have been reported have decreased levels of NKG2D (a major activator receptor), together with impaired degranulation capabilities and reduced production and release of cytolytic molecules, such as perforin, granzymes, and IFNγ (Figure 2I) [136,140].…”

Section: Nk Cellsmentioning

confidence: 99%

The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors

Palano

Gallazzi

Cucchiara

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has been classified as a cold tumor, thus driving the attention in the development of strategies aimed at blocking the infiltration/activation of immunosuppressive cells, while favoring the infiltration/activation of anti-tumor immune cells. Even if immunotherapy has revolutionized the approaches to cancer therapy, there is still a window failure, due to the immune cell plasticity within PCa, that can acquire pro-tumor features, subsequent to the tumor microenvironment (TME) capability to polarize them. This review discussed selected relevant soluble factors [transforming growth factor-beta (TGFβ), interleukin-6 (IL-6), IL-10, IL-23] and cellular components of the innate immunity, as drivers of tumor progression, immunosuppression, and angiogenesis within the PCa-TME.

show abstract

The changing role of natural killer cells in cancer metastasis

Cited by 53 publications

References 151 publications

A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response

A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response

Myeloid-derived suppressor cell dynamics control outcomes in the metastatic niche

The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors

Contact Info

Product

Resources

About