Cell Trafficking at the Intersection of the Tumor–Immune Compartments

Abstract

Migration is an essential cellular process that regulates human organ development and homeostasis as well as disease initiation and progression. In cancer, immune and tumor cell migration is strongly associated with immune cell infiltration, immune escape, and tumor cell metastasis, which ultimately account for more than 90% of cancer deaths. The biophysics and molecular regulation of the migration of cancer and immune cells have been extensively studied separately. However, accumulating evidence indicates that, in the tumor microenvironment, the motilities of immune and cancer cells are highly interdependent via secreted factors such as cytokines and chemokines. Tumor and immune cells constantly express these soluble factors, which produce a tightly intertwined regulatory network for these cells’ respective migration. A mechanistic understanding of the reciprocal regulation of soluble factor–mediated cell migration can provide critical information for the development of new biomarkers of tumor progression and of tumor response to immuno-oncological treatments. We review the biophysical and biomolecular basis for the migration of immune and tumor cells and their associated reciprocal regulatory network. We also describe ongoing attempts to translate this knowledge into the clinic. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 24 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment

“…Our findings that suppression of tumor progression and metastasis by iEF treatment was contingent on an intact immune system led us to analyze the effect of iEFs on the tumor immune microenvironment. The migratory behavior of macrophages can influence tumor progression 32,33 and plays a crucial role in coordinating immune responses and inflammation 34,35 . Thus, we first assessed the direct effect of iEF treatment on immune cell migration.…”

A 3D in vitro assay to study combined immune cell infiltration and cytotoxicity

“…1a, 1). Next, these cells migrate through the tissue’s stromal matrix toward tumor cells via chemokine/cytokine directed chemotaxis and/or random migration [5] (Fig. 1a, 2).…”

“…These assays focus exclusively on proximity-mediated cell recognition and killing by co-seeding immune cells with cancer cells or overlaying immune cells onto a monolayer of cancer cells on a culture plate [9][10][11]. Yet, the ability of immune cells to travel to the tumor site is an essential cellular attribute when evaluating their overall cytotoxic effect in solid tumors [4,5,[12][13][14]. The physical barriers dividing the collagen-rich stromal region from the tumor where cancer cells deposit the components of a basement membrane (i.e., laminins and collagens) cannot be replicated in 2D systems [6][7][8]15].…”

CEACAM1 Is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma

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