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Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Related Experiment Video

Updated: May 31, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
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Published on: March 8, 2022

Breaking the Immune Sanctuary: Targeting Metastatic Niches.

Arjun Ravishankar1, Ganesan Ramamoorthi2, Tobias Weiss3

  • 1Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT.

American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting
|May 28, 2026
PubMed
Summary

Metastasis drives cancer death via immune-protected sanctuaries. Novel strategies like dendritic cell therapy and compartment-directed treatments show promise in overcoming immunosuppression and eradicating cancer cells.

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Area of Science:

  • Oncology
  • Immunology
  • Cancer Metastasis Research

Background:

  • Metastasis is the primary cause of cancer mortality.
  • Disseminated cancer cells (DCCs) form premetastatic niches and immune sanctuaries, evading immune surveillance and therapy.
  • These sanctuaries, particularly in the liver, peritoneum, and CNS, involve organ-specific remodeling and recruitment of immunosuppressive myeloid cells.

Purpose of the Study:

  • To review organ-specific architectural and immunologic remodeling in premetastatic niches.
  • To explore emerging therapeutic paradigms for overcoming niche-specific immunosuppression.
  • To highlight advancements in monitoring metastatic sanctuaries and clinical strategies for targeting them.

Main Methods:

  • Review of organ-specific remodeling in liver, peritoneum, and CNS.
  • Analysis of spatial multi-omics and compartment-specific liquid biopsies (e.g., CSF ctDNA).
  • Evaluation of novel therapeutic strategies including intratumoral cDC1 delivery and compartment-directed CNS therapies.

Main Results:

  • Tumor factors drive fibrovascular changes and recruit suppressive myeloid cells in sanctuaries.
  • Intratumoral cDC1 delivery induces robust CD4+ Th1 immunity, reversing suppression and eradicating DCCs.
  • Compartment-directed CNS strategies and locoregional interventions show promise.

Conclusions:

  • Targeting established sanctuaries requires multimodal strategies integrating systemic agents with locoregional interventions.
  • Clinical trial designs must adapt to clonal evolution and diagnostic confounders.
  • Compartment-specific endpoints are crucial for accurately assessing niche-directed efficacy.