Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment

Sakakura, Koichi; Takahashi, Hideyuki; Kaira, Kyoichi; Toyoda, Minoru; Murata, Takaaki; Ohnishi, Hiroshi; Oyama, Tetsunari; Chikamatsu, Kazuaki

doi:10.1038/labinvest.2016.70

Cited by 65 publications

(47 citation statements)

References 40 publications

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“…This result may be associated with both the antitumor and tumor‐suppressive properties of TAM, and the composition of TAM is different for different stages of OSCC. Unlike the controversial conclusions about the correlations between the total number of macrophages and the prognosis of OSCC, most studies have supported that more M2‐type macrophages indicate a poorer prognosis in OSCC patients (Balermpas et al , ; Fujii et al , ; He et al , ; Hu et al , ; Matsuoka et al , ; Sakakura et al , ; Wang et al , ). Here, we found that the proportion of M2/M1 macrophages, but not the total amount of macrophages, affects the prognosis of OSCC patients.…”

Section: Discussionmentioning

confidence: 99%

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

et al. 2020

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Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor‐associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP‐1 cells, promoted M2‐like macrophage polarization in vitro, and increased the proportion of M2‐like macrophages in a xenograft mouse model. Moreover, both M1‐ and M2‐like macrophage polarization‐associated proteins were induced in macrophages cocultured with RACK1‐silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C‐C motif chemokine 2 (CCL2), C‐C motif chemokine 5 (CCL5), interleukin‐6 (IL‐6), and interleukin‐1 (IL‐1) are closely related to RACK1 expression. In addition, blocking nuclear factor‐kappa B (NF‐κB) could promote M2‐like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2‐like polarization by regulating NF‐κB and could be used as a potential therapeutic target for antitumor immunity.

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Section: Discussionmentioning

confidence: 99%

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

et al. 2020

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“…The presence of CD47 in AML was also associated with a high self-renewal potential of cancer stem cells and with low patient survival (151,152). CD47 overexpression also correlates with poor prognosis in head and neck squamous cell carcinoma, melanoma, and osteosarcoma (153)(154)(155)(156).…”

Section: Impaired Dcs Recruitment: Ccl4 Inhibitionmentioning

confidence: 98%

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

et al. 2019

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WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies.

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“…An immunosuppressive tumor microenvironment can also result from immune modulatory effects of CAF (32), TAM (40), and MDSC (41) (Figure 1). In addition, extracellular signals from angiogenesis can also drive immune suppression by directly suppressing APCs and immune effector cells, or by augmenting the effect of Tregs, MDSC, and TAM.…”

Section: Primary Resistance To Icis In Hnsccmentioning

confidence: 99%

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Kok

2020

Front. Oncol.

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Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell Kok Immune Evasion From PD-1/PD-L1 Immunotherapy immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.

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Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment

Cited by 65 publications

References 40 publications

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF‐κB pathway in oral squamous cell carcinoma

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

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