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Interactions Between Circulating Tumor Cells and the Immune System in Colorectal Cancer: Friends or Foes?

Created on 20 Sep 2026

Authors

Michela De Meo, Chiara Nicolazzo

Published in

Cancers. Volume 18. Issue 13. Jun 29, 2026. Epub Jun 29, 2026.

Abstract

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, mainly due to metastasis. Circulating tumor cells (CTCs) act as the biological "seeds" of dissemination, traveling through the bloodstream to colonize distant organs. However, the blood is a hostile environment where CTCs must constantly face immune pressure. This review explores the bidirectional interactions between CTCs and immune cells in CRC, asking whether CTCs are merely vulnerable targets of immunosurveillance or can exploit the immune system for survival and metastasis. We dissect intrinsic and extrinsic immune evasion mechanisms, including MHC-I modulation, immune checkpoint expression (PD-L1, CD47, FasL), platelet cloaking, and neutrophil extracellular traps (NETs). Furthermore, we examine how CTCs form heterotypic clusters with monocytes, neutrophils, and lymphocytes, creating pro-metastatic niches and promoting phenotypic plasticity. The impact of CTCs on systemic immunity, including reprogramming of NK cells, T lymphocytes, and myeloid-derived suppressor cells (MDSCs), is discussed. Importantly, we highlight the emerging role of CTCs as dynamic biomarkers for immunotherapy, focusing on the predictive value of PD-L1+ CTCs and the potential of CTC-derived neoantigens for personalized vaccination. Despite progress, challenges remain in standardization, detection sensitivity, and clinical validation. Understanding the equilibrium between immune elimination and evasion by CTCs is crucial to develop novel interventions that interrupt the metastatic dialog and improve outcomes for CRC patients.

PMID:
42449648
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.

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