Dataset Information

Tissue localization of Natural Killer Cell cells dictates surveillance of lung metastasis

ABSTRACT: The lung is a common metastatic site for various cancer types. Successful immune surveillance of lung metastasis depends on Natural Killer (NK) cells, but the underlying mechanisms are elusive. Here, we show that the pulmonary vasculature recruits and maintains highly cytotoxic and differentiated CD11bhigh NK cells through the integrins Lymphocyte Function-associated Antigen 1 (LFA-1) and Very Late Antigen (VLA-4). These NK cells rapidly eradicate metastasizing tumor cells within the vasculature. However, after the initial clearing phase, pulmonary NK cells fail to track extravasated tumor cells and remain intravascular, outside of the emerging nodules. In contrast, metastatic nodules are preferentially infiltrated with bloodborne and less differentiated CD27high NK cells. Within the metastatic lung, CD11bhigh NK cells undergo a rapid impairment of their migratory and cytotoxic features, while the intranodular CD27high subset transitions towards a transforming growth factor β (TGF-β)-driven state with reduced capacity to persist in the tumor tissue. Our findings demonstrate that the compartmentalization of NK cells is key for effective tumor cell surveillance in lung metastasis and that the use of TGF-β-resistant CD27high NK cells might be a novel strategy to enhance local anti-tumor activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE301222 | GEO | 2025/09/08

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background Epithelial to mesenchymal transition (EMT) endows cancer cells with pro-metastatic properties, which appear most effective when cells enter an intermediate hybrid (H) state, characterized by integrated mesenchymal (M) and epithelial (E) traits. The reasons for this advantage are poorly known and, especially, it is totally unexplored whether the interplay between H-cells and NK cells could have a role. Here we characterize the pro-metastatic mechanics of Non-small Cell Lung Cancer (NSCLC) H-cells and their subset of cancer-initiating cells (CICs), dissecting crucial interactions with NK cells. Methods Human lung cancer cell lines and sub-lines representative of E, M, or H states, assessed by proteomics, were analysed in vivo for their tumor-forming and disseminating capabilities. Interactions with NK cells were investigated in vitro using migration assays, cytotoxic degranulation assays and evaluation of CD133+ CICs modulation after co-culture, and validated in vivo through NK cell neutralization assays. Correlation between EMT status, NK cell infiltration, and survival data, was evaluated in a cohort of surgically resected NSCLC cases (n=79). Results We demonstrated that H-cells, have limited dissemination capability but show highest potential to initiate metastases in vivo. This property was related to their ability to escape NK cell surveillance. Mechanistically, H-cells expressed low levels of NK-attracting chemokines (CXCL1 and CXCL8), generating poorly infiltrated metastases. Accordingly, proteomics and GO enrichment analysis of E, H, M cell lines showed that the related secretory processes could change during EMT. Furthermore, H-CICs uniquely expressed high levels of the inhibitory ligand B7-H3, which protected H-CIC from NK cell-mediated clearance. In vivo neutralization assays confirmed that, indeed, the pro-metastatic properties of H-cells are poorly controlled by NK cells. Finally, the analysis of patients revealed that detection of hybrid phenotypes associated with low NK infiltration in NSCLC clinical specimens could identify a subset of patients with poor prognosis. Conclusions Our study demonstrates that H-cells play a central role in the metastatic spread in NSCLC. Such pro-metastatic advantage of H-cells is supported by their altered interaction with NK cells and by the critical role of B7H3 in preserving their H-CIC component, indicating B7H3 as a potential target in combined NK-based therapies.

Dataset Information

Tissue localization of Natural Killer Cell cells dictates surveillance of lung metastasis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets