Poor patient outcome correlates with active engulfment of cytokeratin positive CTCs within cancer-associated monocyte population in lung cancer

Poor patient outcome correlates with active engulfment of cytokeratin positive CTCs within cancer-associated monocyte population in lung cancer

High rates of mortality in non-small cell lung cancer lung cancer is due to inherent and acquired resistance to systemic therapies and subsequent metastatic burden. Metastasis is supported by suppression of the immune system at secondary organs and within the circulation. Modulation of the immune sy...

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Bibliographic Details
Published in:Clinical & experimental metastasis Vol. 41; no. 3; pp. 219 - 228
Main Authors: Wiegmans, A. P., Ivanova, E., Naei, V. Y., Monkman, J., Fletcher, J., Mullally, W., Warkiani, M. E., O’Byrne, K., Kulasinghe, A.
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 2024
Springer Nature B.V
Subjects:
Biomarkers
Biomedical and Life Sciences
Biomedicine
Biopsy
Cancer Research
Chemotherapy
Circulation
Clinical outcomes
Correlation
Cytokeratin
Hematology
Immune checkpoint inhibitors
Immune system
Inhibitors
Lung cancer
Metastases
Metastasis
Monocytes
Non-small cell lung carcinoma
Oncology
Patients
Real time
Small cell lung carcinoma
Surgical Oncology
Therapeutic targets
Tumors
Tumour associated monocytes (TAM)
Circulating tumour cells (CTCs)
Leucocyte common antigen
Cancer-associated macrophage-like cells (CAMLs)
Lung cancer
Cytokeratins
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Summary:High rates of mortality in non-small cell lung cancer lung cancer is due to inherent and acquired resistance to systemic therapies and subsequent metastatic burden. Metastasis is supported by suppression of the immune system at secondary organs and within the circulation. Modulation of the immune system is now being exploited as a therapeutic target with immune checkpoint inhibitors. The tracking of therapeutic efficacy in a real-time can be achieved with liquid biopsy, and evaluation of circulating tumour cells and the associated immune cells. A stable liquid biopsy biomarker for non-small cell lung cancer lung cancer has yet to be approved for clinical use. We performed a cross-sectional single-site study, and collected liquid biopsies from patients diagnosed with early, locally advanced, or metastatic lung cancer, undergoing surgery, or systemic therapy (chemotherapy/checkpoint inhibitors). Evaluation of overall circulating tumour cell counts, or cluster counts did not correlate with patient outcome. Interestingly, the numbers of Pan cytokeratin positive circulating tumour cells engulfed by tumour associated monocytes correlated strongly with patient outcome independent of circulating tumour cell counts and the use of checkpoint inhibitors. We suggest that Pan cytokeratin staining within monocytes is an important indicator of tumour-associated inflammation post-therapy and an effective biomarker with strong prognostic capability for patient outcome.
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ISSN:0262-0898
1573-7276
1573-7276
DOI:10.1007/s10585-024-10270-w