Role Of Cell Adhesion Molecules Research Articles

The role of adhesion molecules in osteocalcin-induced effects on glucose and lipid metabolism in adipocytes

Recent findings suggest that uncarboxylated osteocalcin (GluOC) promotes glucose and lipid metabolism via its putative receptor GPRC6A; however, its direct effect on adipocytes remains elusive. In this study, we elucidated the effects of GluOC on adipocytes, with an emphasis on the role of cell adhesion molecules. We determined that GluOC promoted the expression of adipocyte adhesion molecule (ACAM) and its transcription factor Krüppel-like factor 4 and enhanced the cortical actin filament assembly, which ameliorated lipid droplet hypertrophy. Additionally, GluOC upregulated the expression of integrin αVβ3 and activation of focal adhesion kinase (FAK) and prevented insulin receptor substrate 1 (IRS1) degradation by inhibiting the ubiquitin–proteasome system via the FAK–PLC–PKC axis, which activated IRS1–Akt-mediated glucose transporter 4 (GLUT4) transport. Furthermore, we showed that GluOC elevated the expression of the insulin-independent glucose transporters GLUT1 and GLUT8, which facilitated insulin stimulation-independent glucose transport. The GluOC-induced activation of integrin αVβ3 signaling promoted microtubule assembly, which improved glucose and lipid metabolism via its involvement in intracellular vesicular transport. GluOC treatment also suppressed collagen type 1 formation, which might prevent adipose tissue fibrosis in obese individuals. Overall, our results imply that GluOC promotes glucose and lipid metabolism via ACAM, integrin αVβ3, and GLUT1 and 8 expression, directly affecting adipocytes.

Role of Cell Adhesion Molecules in Extravasation of Lymphocytes in Immunized Animals

Role of Cell Adhesion Molecules in Extravasation of Lymphocytes in Immunized Animals

CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice.

Methamphetamine (Meth), a commonly used central nervous system stimulant, is highly addictive. Currently, there is no effective treatment for Meth dependence and abuse, although cell adhesion molecules (CAMs) have been shown to play an important role in the formation and remodeling of synapses in the nervous system while also being involved in addictive behavior. Contactin 1 (CNTN1) is a CAM that is widely expressed in the brain; nevertheless, its role in Meth addiction remains unclear. Therefore, in the present study, we established mouse models of single and repeated Meth exposure and subsequently determined that CNTN1 expression in the nucleus accumbens (NAc) was upregulated in mice following single or repeated Meth exposure, whereas CNTN1 expression in the hippocampus was not significantly altered. Intraperitoneal injection of the dopamine receptor 2 antagonist haloperidol reversed Meth-induced hyperlocomotion and upregulation of CNTN1 expression in the NAc. Additionally, repeated Meth exposure also induced conditioned place preference (CPP) in mice and upregulated the expression levels of CNTN1, NR2A, NR2B, and PSD95 in the NAc. Using an AAV-shRNA-based approach to specifically silence CNTN1 expression in the NAc via brain stereotaxis reversed Meth-induced CPP and decreased the expression levels of NR2A, NR2B, and PSD95 in the NAc. These findings suggest that CNTN1 expression in the NAc plays an important role in Meth-induced addiction, and the underlying mechanism may be related to the expression of synapse-associated proteins in the NAc. The results of this study improved our understanding of the role of cell adhesion molecules in Meth addiction.

Physicochemical Principles of Adhesion Mechanisms in the Brain

The brain functions through neuronal circuits and networks that are synaptically connected. This type of connection can exist due to physical forces that interact to stabilize local contacts in the brain. Adhesion is a fundamental physical phenomenon that allows different layers, phases, and tissues to connect. Similarly, synaptic connections are stabilized by specialized adhesion proteins. This review discusses the basic physical and chemical properties of adhesion. Cell adhesion molecules (CAMs) such as cadherins, integrins, selectins, and immunoglobulin family of cell adhesion molecules (IgSF) will be discussed, and their role in physiological and pathological brain function. Finally, the role of CAMs at the synapse will be described. In addition, methods for studying adhesion in the brain will be presented.

Identification of subtypes of hepatocellular carcinoma and screening of prognostic molecular diagnostic markers based on cell adhesion molecule related genes.

Cell adhesion molecules can predict liver hepatocellular carcinoma (LIHC) metastasis and determine prognosis, while the mechanism of the role of cell adhesion molecules in LIHC needs to be further explored. LIHC-related expression data were sourced from The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) databases, and genes related to cell adhesion were sourced from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. First, the TCGA-LIHC dataset was clustered by the nonnegative matrix factorization (NMF) algorithm to find different subtypes of LIHC. Then the difference of prognosis and immune microenvironment between patients of different subtypes was evaluated. In addition, a prognostic risk model was obtained by least shrinkage and selection operator (LASSO) and Cox analysis, while a nomogram was drawn. Furthermore, functional enrichment analysis between high and low risk groups was conducted. Finally, the expressions of model genes were explored by quantitative real-time polymerase chain reaction (qRT-PCR). The 371 LIHC patients were classified into four subtypes by NMF clustering, and survival analysis revealed that disease-free survival (DFS) of these four subtypes were clearly different. Cancer-related pathways and immune microenvironment among these four subtypes were dysregulated. Moreover, 58 common differentially expressed genes (DEGs) between four subtypes were identified and were mainly associated with PPAR signaling pathway and amino acid metabolism. Furthermore, a prognostic model consisting of IGSF11, CD8A, ALCAM, CLDN6, JAM2, ITGB7, SDC3, CNTNAP1, and MPZ was built. A nomogram consisting of pathologic T and riskScore was built, and the calibration curve illustrated that the nomogram could better forecast LIHC prognosis. Gene Set Enrichment Analysis (GSEA) demonstrated that DEGs between high and low risk groups were mainly involved in cell cycle. Finally, the qRT-PCR illustrated the expressions of nine model genes between normal and LIHC tissue. A prognostic model consisting of IGSF11, CD8A, ALCAM, CLDN6, JAM2, ITGB7, SDC3, CNTNAP1, and MPZ was obtained, which provides an important reference for the molecular diagnosis of patient prognosis.

The role of cell adhesion molecules in the inflammatory process and development of gastric and duodenal peptic ulcer disease, their molecular genetic determinants

With gastric and duodenal peptic ulcer disease, a chronic inflammatory process develops, in which cell adhesion molecules are actively involved. Currently, as a result of genome-wide association studies (GWAS), more than 20 polymorphic variants involved in determining their level have been identified, including rs505922 of the ABO gene. At the same time, this polymorphic variant, according to GWAS, is associated with an increased risk of developing peptic ulcer disease (PUD). It should also be noted that the association of the O(I) blood group according to the ABO system with an increased risk of developing PUD has long been known. Therefore, the genetic determinants of cell adhesion molecules are of interest for studying as candidate genes for peptic ulcer disease.

The role of cell adhesion molecules in the progression of bladder urothelial carcinomas.

Alteration of the intercellular adhesion system plays an essential role in the initiation and progression of bladder carcinomas. We followed the immunoexpression of adhesion molecules, E-cadherin, β-catenin and Claudin-1, in relation to the histopathological grade and the pT category in a number of 50 urothelial carcinomas of the bladder, based on a final staining score (FSS), calculated on the basis of reaction intensity and labeled cells number. E-cadherin immunoexpression was identified in the membrane of tumor cells, low FSS being associated with invasive high-grade carcinomas. β-catenin reactions were membranous in the case of low-grade noninvasive carcinomas and predominantly cytoplasmic and nuclear in the case of high-grade invasive ones, for which high FSS were associated. Claudin-1 was identified at the membrane level, the high FSS values being more frequent in the case of high-grade invasive carcinomas, although there were no significant statistical associations. Loss of E-cadherin expression and the associated positive linear relation of β-catenin and Claudin-1 indicate the usefulness of the analyzed markers in identifying the invasive aggressive phenotype of urothelial bladder carcinomas.

OP-8 - Reduced expression of cell adhesion molecules affected by high abdominal temperature results in abnormal spermatogenesis in the cryptorchidism model mice

Cryptorchidism is one of the common causes of congenital abnormality in human. The higher temperature than scrotum disrupts normal spermatogenesis and results in male infertility. However, this molecular mechanism is still unknown. The cell adhesion molecules between spermatogenic and Sertoli cells are essential for spermatogenesis as well as endocrine and local factors. We demonstrated the roles of cell adhesion molecules in abnormal spermatogenesis of cryptorchid testes. We used the cryptorchidism model mice undergone surgical translocation of left testis into abdominal cavity. Mice were undergone for cryptorchidism of left testis at 0 day (D) and examined at 3, 5, 7, 14, 21, and 28D post-operatively. The paraffin sections were stained by hematoxylin and eosin. The expression of cell adhesion molecules Cadm1, Nectin-2, Nectin-3 and cleaved caspase-3 in testes was examined by immunohistochemistry and western blot analysis. Further, Transmission electron microscopy is used to observe the ultrastructure of cryptorchid testis. The detached spermatogenic cells and abnormal acrosomes were observed in cryptorchid testes after 5D, multinucleated giant cells appeared at 7D, and then seminiferous tubules atrophied after 21D. Many degenerating and a few apoptotic cells were observed in cryptorchid testes after 21D.The expression of Cadm1, Nectin-2, and Nectin-3 decreased in seminiferous tubules by immunohistochemistry and western blot analysis. Ultrastructural observation of cryptorchid testes revealed multinucleated giant cells were derived from spermatogonia, spermatocytes, or spermatids. The higher abdominal temperature affected normal spermatogenesis by disrupted the expression of Cadm1, Nectin-2 and Nectin-3 in testes.

Selectins and their involvement in the pathogenesis of cardiovascular diseases

The review presents current data on the structure and functional role of cell adhesion molecules belonging to the selectin family (selectins P, L and E), and their involvement in the pathogenesis of cardiovascular diseases. On the one hand, intercellular adhesion molecules of the vascular wall endothelium, platelets and leukocytes are an important link in the processes of vasculogenesis, development and regeneration of the vascular system. On the other hand, these molecules participate in the earliest stages of endothelial dysfunction with the subsequent development of pathology. For this reason, figuring out the mechanisms of activity of this group of molecules is very important for understanding the molecular basis of the cardiovascular diseases pathogenesis. The adhesion of molecules, both between cells and between cells and a component of the extracellular matrix, is the most important stage of physiological and biochemical processes. According to present knowledge, five classes of intercellular adhesion molecules are known: integrins, cadherins, immunoglobulins (including nectins), selectins and addressins. All of them are bonded to a cytoplasmic membrane and provide the interaction of cells with each other. Some of them are transmembrane and associated with the cytoskeleton of the cell. On the cell surface, intercellular adhesion molecules can be located in clusters, forming multipoint binding sites and thereby determining the degree of avidity. One of the most significant functions of selectins is participation in the initial stage of the leukocyte adhesion cascade, which results in their binding to the endothelium, rolling and further extravasation into tissues. The first stage of this process is mediated by specific non-covalent interactions between selectins and their glycan ligands, with the glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains one of the main strategies aimed at developing new methods of treating immune, inflammatory and oncological diseases.

Endoglycan Regulates Purkinje Cell Migration by Balancing Cell-Cell Adhesion.

The importance of cell adhesion molecules for the development of the nervous system has been recognized many decades ago. Functional in vitro and in vivo studies demonstrated a role of cell adhesion molecules in cell migration, axon growth and guidance, as well as synaptogenesis. Clearly, cell adhesion molecules have to be more than static glue making cells stick together. During axon guidance, cell adhesion molecules have been shown to act as pathway selectors but also as a means to prevent axons going astray by bundling or fasciculating axons. We identified Endoglycan as a negative regulator of cell-cell adhesion during commissural axon guidance across the midline. The presence of Endoglycan allowed commissural growth cones to smoothly navigate the floor-plate area. In the absence of Endoglycan, axons failed to exit the floor plate and turn rostrally. These observations are in line with the idea of Endoglycan acting as a lubricant, as its presence was important, but it did not matter whether Endoglycan was provided by the growth cone or the floor-plate cells. Here, we expand on these observations by demonstrating a role of Endoglycan during cell migration. In the developing cerebellum, Endoglycan was expressed by Purkinje cells during their migration from the ventricular zone to the periphery. In the absence of Endoglycan, Purkinje cells failed to migrate and, as a consequence, cerebellar morphology was strongly affected. Cerebellar folds failed to form and grow, consistent with earlier observations on a role of Purkinje cells as Shh deliverers to trigger granule cell proliferation.

The role of cell adhesion molecules (ICAM-1 and VCAM-1) in acute ischemic stroke

The role of cell adhesion molecules (ICAM-1 and VCAM-1) in acute ischemic stroke

To Stick or Not to Stick: The Multiple Roles of Cell Adhesion Molecules in Neural Circuit Assembly.

Precise wiring of neural circuits is essential for brain connectivity and function. During development, axons respond to diverse cues present in the extracellular matrix or at the surface of other cells to navigate to specific targets, where they establish precise connections with post-synaptic partners. Cell adhesion molecules (CAMs) represent a large group of structurally diverse proteins well known to mediate adhesion for neural circuit assembly. Through their adhesive properties, CAMs act as major regulators of axon navigation, fasciculation, and synapse formation. While the adhesive functions of CAMs have been known for decades, more recent studies have unraveled essential, non-adhesive functions as well. CAMs notably act as guidance cues and modulate guidance signaling pathways for axon pathfinding, initiate contact-mediated repulsion for spatial organization of axonal arbors, and refine neuronal projections during circuit maturation. In this review, we summarize the classical adhesive functions of CAMs in axonal development and further discuss the increasing number of other non-adhesive functions CAMs play in neural circuit assembly.

Cell Adhesion Molecules in Neuroblastoma: Complex Roles, Therapeutic Potential.

Neuroblastoma, a biologically heterogeneous tumor derived from neural crest cells, accounts for approximately 15% of childhood deaths from cancer. Recently, scientific literature has explored the role of cell adhesion molecules (CAMs) in cancer metastasis through cell detachment, migration, and invasion. Through a review of the current literature, it is evident that expression of different CAMs on neuroblastoma tumors is associated with favorable or unfavorable clinical prognosis. In patients diagnosed with neuroblastoma, treatment strategies include chemotherapy, surgery, radiotherapy, stem cell transplant, and more recently, immunotherapy and other targeted therapies. Long term survival remains poor despite multimodality treatment, especially for children with high-risk neuroblastoma, making it more necessary to explore innovative targeted therapies. CAMs have immense potential as therapeutic targets, but there is a need for growth and scientific exploration before CAM therapies become clinically useful.

Using Immortalized Endothelial Cells to Study the Roles of Adhesion Molecules in VEGF-Induced Signaling.

The ability to study the role of specific genes in endothelial cell biology is made possible by our ability to modulate their expression through siRNA or knockout technologies. However, many in vitro protocols, particularly those of a biochemical nature, require large numbers of endothelial cells. These types of analyses are encumbered by the need to repeatedly produce and characterize primary endothelial cell cultures and can be greatly facilitated by the use of immortalized microvascular endothelial cells. However, we have found that the manipulation of gene expression in these cells is not always straight forward. Here we describe how we alter gene expression in polyoma middle T antigen immortalized microvascular endothelial cells isolated from wild-type and genetically modified mice to study the role of cell adhesion molecules in downstream assays.

Platelet-mediated tumor metastasis mechanism and the role of cell adhesion molecules.

Mounting evidence suggests that platelets play an essential role in cancer metastasis. The interactions between platelets and circulating tumor cells (CTCs) promote cancer metastasis. CTCs induce platelet activation and aggregation, and activated platelets gather and protect CTCs from shear stress and natural killer cells. Finally, platelets stimulate CTC anoikis resistance, epithelial-to-mesenchymal transition, angiogenesis, extravasation, and eventually, metastasis. Cell adhesion molecules (CAMs) have been identified as active players during the interaction of CTCs with platelets, but the specific mechanism underlying the contribution of platelet-associated CAMs to CTC metastasis remains unclear. In this review, we introduce the mechanism of platelet-related tumor metastasis and particularly focus on the role of CAMs in it.

Biocompatibility pathways and mechanisms for bioactive materials: The bioactivity zone

This essay analyzes the scientific evidence that forms the basis of bioactive materials, covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of biomaterials. This is a detailed assessment of performance in areas such as bone-induction, cell adhesion, immunomodulation, thrombogenicity and antimicrobial behavior. Bioactivity is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host tissue. Although the term ‘bioactive material’ is widely used and has a well understood general meaning, it would be useful now to concentrate on this interfacial region, considered as ‘the bioactivity zone’. Bioactivity phenomena are either due to topographical/micromechanical characteristics, or to biologically active species that are presented in the bioactivity zone. Examples of topographical/micromechanical effects are the modulation of the osteoblast – osteoclast balance, nanotopographical regulation of cell adhesion, and bactericidal nanostructures. Regulation of bioactivity by biologically active species include their influence, especially of metal ions, on signaling pathways in bone formation, the role of cell adhesion molecules and bioactive peptides in cell attachment, macrophage polarization by immunoregulatory molecules and antimicrobial peptides. While much experimental data exists to demonstrate the potential of such phenomena, there are considerable barriers to their effective clinical translation. This essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials, especially when the material is modified in a manner designed to specifically induce that activity.

A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer.

Androgen deprivation therapy or ADT is one of the cornerstones of management of locally advanced or metastatic prostate cancer, alongside radiation therapy. However, despite early response, most advanced prostate cancers progress into an androgen unresponsive or castrate resistant state, which hitherto remains an incurable entity and the second leading cause of cancer-related mortality in men in the US. Recent advances have uncovered multiple complex and intermingled mechanisms underlying this transformation. While most of these mechanisms revolve around androgen receptor (AR) signaling, novel pathways which act independently of the androgen axis are also being discovered. The aim of this article is to review the pathophysiological mechanisms that help bypass the apoptotic effects of ADT to create castrate resistance. The article discusses castrate resistance mechanisms under two categories: 1. Direct AR dependent pathways such as amplification or gain of function mutations in AR, development of functional splice variants, posttranslational regulation, and pro-oncogenic modulation in the expression of coactivators vs corepressors of AR. 2. Ancillary pathways involving RAS/MAP kinase, TGF-beta/SMAD pathway, FGF signaling, JAK/STAT pathway, Wnt-Beta catenin and hedgehog signaling as well as the role of cell adhesion molecules and G-protein coupled receptors. miRNAs are also briefly discussed. Understanding the mechanisms involved in the development and progression of castration-resistant prostate cancer is paramount to the development of targeted agents to overcome these mechanisms. A number of targeted agents are currently in development. As we strive for more personalized treatment across oncology care, treatment regimens will need to be tailored based on the type of CRPC and the underlying mechanism of castration resistance.

Cell Adhesion Molecules are Upregulated and May Drive Inflammation in Chronic Rhinosinusitis with Nasal Polyposis.

PurposeChronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology.Materials and MethodsA prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns.ResultsIntegrin and ICAM genes were significantly elevated in the blood (p<0.001 to p<0.05) and sinuses (p<0.0003 to p<0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (p<0.01 to p<0.05) and sinuses (p<0.01) were observed between ITGAM, ITGAX, ITGB2, and ICAM3. ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (p<0.0001 to p<0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (p<0.02).ConclusionThe systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.

Differential Expression of CADM1 in Gastrointestinal Stromal Tumors of Different Sites and with Different Gene Abnormalities.

Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined CADM1 expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c-kit mutation than gastric GISTs with exon 11 c-kit mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c-kit mutation showed significantly higher CADM1 mRNA than gastric GISTs with exon 11 c-kit mutation. Although most small intestinal GISTs showed high CADM1 mRNA expression regardless of gene abnormality types, different CADM1 expression was detected between gastric GISTs with c-kit mutation and those with PDGFRA mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high CADM1expression in small intestinal GISTs might be acquired during tumorigenesis. Different CADM1 expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment.

Simple SummaryImmunotherapy improved the therapeutic landscape for patients with advanced cancer diseases. However, many patients do not benefit from immunotherapy. The bidirectional crosstalk between myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) contributes to immune evasion, limiting the success of immunotherapy by checkpoint inhibitors. This review aims to outline the current knowledge of the role and the immunosuppressive properties of MDSC and Treg within the tumor microenvironment (TME). Furthermore, we will discuss the importance of the functional crosstalk between MDSC and Treg for immunosuppression, issuing particularly the role of cell adhesion molecules. Lastly, we will depict the impact of this interaction for cancer research and discuss several strategies aimed to target these pathways for tumor therapy.Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.