Molecular Mechanisms, Diagnosis and Targeted Treatment in Lymphatic Metastasis of Cancers

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Background

Lymph node (LN) metastasis is the first and main metastatic pattern of epithelial tumors, including bladder, breast, colon cancers and so on. Importantly, LN metastasis is the main cause of death and is a key clinical problem in cancers. It is a complex multistep process that involves dissemination of cancer cells to lymphatic vessels which also interact with immune effectors that have tumour surveillance function; followed by transport, settlement, and colonization expansion of cancer cells in the LNs which can be seen as a form of the pre-metastatic niche.

There has been an increase in understanding the role of tertiary lymphoid structure (TLS) in tumours, which has the same heterotypic immune cellular composition as lymph nodes, in deciding the efficacy of cancer immunotherapy. It remains unclear whether the immune cell components from these TLS can traffic towards the lymph nodes and modify the premetastatic microenvironment there, and how immune checkpoint therapies (e.g. αCTLA-4) may affect such cell movement.

Although several sets of chemokines and their receptors have been reported to be associated with the LN metastasis, the precise molecular mechanisms, which will inevitably involve heterotypic cell interactions at different stages of the cancer metastatic cascade, remain largely unknown. It is urgent to broaden our understanding of LN metastatic mechanisms which will greatly improve the development of strategies of diagnoses and therapies in the era of precision oncology.

In this Research Topic, we plan to solicit further research into the mechanisms of crosstalk between tumor cells and microenvironment in LN metastasis of cancers, including chemokines, exosomes, lymphangiogenesis, and epigenetic regulators (non-coding RNAs, DNA methylation, post-translational modifications of histones, etc.).

Importantly, we will invite contributions that will exemplify the organ-specific spatial distribution of these heterotypic intercellular communications (e.g. differences between TLS and draining lymph nodes). The utility of spatial mapping techniques such as imaging CYTOF, will be discussed.
In order to enhance translation research, this Research Topic will also focus on novel and recent advances in the molecular diagnosis, novel applications of new or current cancer therapeutics targeting LN metastasis. We will explore how these mechanisms that regulate lymph node metastasis (such as VEGF-C) may impact on the efficacy of immunotherapy including immune checkpoint blockade. We envisage that such emerging strategies can be utilized for precision medicine which will help achieve long-lasting disease control and provide survival benefits to patients with advanced cancers.

For this Research Topic, we are interested in Original Research articles, Review articles, Mini-Review articles, Opinion articles and Brief Research Report articles that focus on the following topics:
• The mechanisms of crosstalk between tumor cells and microenvironment in LN metastasis of cancers, including chemokines, exosomes, lymphangiogenesis, and epigenetic regulators (non-coding RNAs, DNA methylation, post-translational modifications of histones, etc.).
• Immunological repertoire between primary tumour and metastatic lymph nodes – similarity/differences and cause/effect relationship.
• The interplay between tertiary lymphoid structure (TLS), heterotypic immune cell interactions in these structures and metastasis (including the phenomenon of premetastatic niche).
• The role of lymphangiogenesis/lymphatic metastatic mechanisms in determining immune checkpoint therapy efficacy
• Molecular markers, materials or arrays to diagnose or predict lymphatic metastasis in cancer patients
• Molecular drugs, antibody or nanotechnology to inhibit lymphatic metastasis or killing metastatic cancer cells

Keywords: Lymphatic Metastasis, Microenvironment, Molecular Diagnostics, Targeted Treatment including Immunotherapy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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