CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma

Abstract

Purpose This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). Methods We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. Results In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. Conclusion CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

A radiomics model to predict γδ T‐cell abundance and overall survival in head and neck squamous cell carcinoma

“…For example, chemokine receptors such as CCR7 and CXCR3 attract specific subsets of immune cells to the tumor site. 40,41 IL-33, a pleiotropic cytokine in HNSCC, modulates immune cells within the TME, including CD4+ T-helper cells, CD8+ T cells, NK cells, DCs, and macrophages. 42 Growing evidence indicates that the composition of tumor-infiltrating lymphocytes, including T cells, B cells, NK cells, macrophages, neutrophils, and MDSCs, is crucial in HNSCC progression, anti-tumor immune response, and patient outcomes.…”

“…Cytokines and chemokines secreted by tumor cells, stromal cells, and immune cells within the TME influence immune cell recruitment and activation. For example, chemokine receptors such as CCR7 and CXCR3 attract specific subsets of immune cells to the tumor site 40,41 . IL‐33, a pleiotropic cytokine in HNSCC, modulates immune cells within the TME, including CD4+ T‐helper cells, CD8+ T cells, NK cells, DCs, and macrophages 42 .…”

Development and Validation of an Individualized Immune Prognostic Signature in HNSCC

“…In addition, in recent study, pirfenidone was regarded as potential drug in suppressing invasion and potentially metastasis in breast cancer [13]. Tumor-associated macrophages (TAMs) also could be induced M2-polarization by cytokines released by tumor cells [43]. Thus, the prognosis of tumor patients may not only due to the changes expression of genes in tumor cells but also tumor microenvironment especially the stromal composition of the HNSCC, which maybe provide a newly clinical intervention.…”

Serine and one-carbon metabolism sustain non-melanoma skin cancer progression

“…For this reason, several clinical and/or pathological parameters have been indicated to predict prognosis, recurrence, and survival, and to drive the therapeutic choice [31][32][33][34][35][36][37]. Notably, cSCCs and HNSCCs display hallmarks of solid tumors mildly responsive to systemic immunotherapy [38][39][40][41][42][43][44][45]. Thus, immunotherapy with PD-1 blockade has emerged as the latest standard-of-care treatment strategy developed for advanced and metastatic SCCs.…”