Targeting tumor-associated macrophages in head and neck squamous cell carcinoma

Li, Bolei; Ren, Min; Han, Qi; Cheng, Lei

doi:10.1016/j.oraloncology.2020.104723

Cited by 45 publications

(39 citation statements)

References 111 publications

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“…PD-L1 can inhibit T-cell activation and contribute to tumour immune evasion in many cancers, like liver cancer and mammary cancer, and macrophages that in ltrate into liver cancers can express higher levels of PD-L1; therefore, we assumed that the same trend would occur in OSCC. [32][33][34] In this study, we found that the macrophages that in ltrated into ER-stressed OSCC tissues expressed high levels of PD-L1 and that the PD-L1 levels were negatively correlated with overall survival. Macrophages are classi ed into M1 and M2 macrophages, where M1 macrophages play a protective role and M2 macrophages promote tumour growth.…”

Section: Discussionmentioning

confidence: 52%

Endoplasmic Reticulum Stress Promotes The Release of Exosomal PD-L1 From Head and Neck Cancer Cells and Facilitates M2 Macrophage Differentiation

Yuan

Jiao

Wang

et al. 2021

Preprint

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Background Endoplasmic reticulum stress (ER stress) fosters cancer cell escape from immune surveillance and upregulate PD-L1 expression, but the mechanisms remain unclear. Methods We analyzed protein levels by immunofluorescence and Western blotting, RNA levels by qRT-PCR. Exosomes were injected intravenously through the tail vein into 6-week-old nude mice once every other day for a total of 10 injections Results Expression of some ER stress markers, including GRP78 (glucose-regulated protein 78), ATF6 (activating transcription factor 6) and PERK (PKR-like endoplasmic reticulum kinase), was upregulated in OSCC tissues and correlated with poor overall survival. The level of ER stress-related proteins positively correlated with a cluster of PD-L1 expression and macrophage infiltration in OSCC tissues. PD-L1 expression in OSCC tissues was negatively correlated with cumulative survival. Incubation with Exo-ER upregulated PD-L1 levels in macrophages in vitro and vivo, and upregulation of PD-L1 promoted macrophage polarisation towards the M2 subtype. Conclusions ER stress induced exosome secretion by OSCC cells and PD-L1 expression in macrophages to promote M2 macrophage differentiation. A novel exosome-modulated mechanism was delineated for OSCCs-macropahge crosstalk that drove tumor growth and should be explored for its therapeutic utility.

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Section: Discussionmentioning

confidence: 52%

Endoplasmic Reticulum Stress Promotes The Release of Exosomal PD-L1 From Head and Neck Cancer Cells and Facilitates M2 Macrophage Differentiation

Yuan

Jiao

Wang

et al. 2021

Preprint

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“…Most DEGs were enriched in pathways related to immunity and inflammation, which indicates that the malignant transformation of oral cancer may be closely related to dysfunction of the immune system and inflammation. Similarly, Cheng et al 29 found that tumor‐associated macrophages (TAMs) are associated with poorer prognosis in HNSCC, and TAMs could promote cancer progression and inhibit the immune response through adaptive and innate immune mechanisms. Chan et al 30 discovered that OSCC was usually accompanied by inflammation and high levels of oxidative stress.…”

Section: Discussionmentioning

confidence: 97%

“…et al29 found that tumor-associated macrophages (TAMs) are associated with poorer prognosis in HNSCC, and TAMs could promote cancer progression and inhibit the immune response through adaptive and innate immune mechanisms. Chan et al 30 discovered that OSCC was usually accompanied by inflammation and high levels of oxidative stress.…”

mentioning

confidence: 99%

Animal model and bioinformatics analyses suggest the TIMP1/MMP9 axis as a potential biomarker in oral squamous cell carcinoma

Wei

et al. 2020

Molecular Carcinogenesis

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Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. However, the molecular mechanism underlying its development and progression is yet unclear. Genes that are differentially expressed, that is, differentially expressed genes (DEGs), between normal and diseased tissues are believed to be involved in disease development and progression. To identify the DEGs in OSCC and explore their role in occurrence and progression, we established a Chinese hamster OSCC model, determined the DEG, screened the identified DEGs, and performed Gene Ontology (GO) and KEGG enrichment analyses. A protein-protein interaction (PPI) network was generated to screen potential candidate genes. We then analyzed the expression, tumor stage and prognosis of candidate genes using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, we verified the candidate DEGs by quantitative real-time PCR and Gene Expression Omnibus analysis. The results showed 194 significantly DEGs, 140 enriched GO terms, and 8 KEGG pathways, which suggested that OSCC was closely related to the immune system, cell migration, and extracellular matrix. GEPIA and PPI network analysis revealed that SPP1, TNC, and ACTA1 were significantly related to tumor staging; SPP1, tissue inhibitors of matrix metallopeptidases (MMPs) 1 (TIMP1), and ACTA1 were closely related to prognosis. The scores for the top five highest degree genes were close, and the TIMP1/MMP9 axis appeared to be at the center of the PPI network, indicating that expression changes in the TIMP1/MMP9 axis and related genes may be involved in tumor invasion and metastasis. These findings provide novel insights into the mechanism of oral cancer.

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“…By depleting the immunosuppressive function or evoking anti-tumor ability, therapeutic strategies targeting TAMs show promising preclinical and clinical effects. Now, macrophage-centered therapeutic approaches such as anti-PD-1 T-cell, targeted therapeutics that can reactivate antitumor T-cell responses, are entering the clinical arena [154,157].…”

Section: Hsv-1 (Herpes Simplex Virus Type 1)mentioning

confidence: 99%

Oral Cancer: A Historical Review

Inchingolo

Santacroce

Ballini

et al. 2020

IJERPH

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Aim: This historical medical literature review aims at understanding the evolution of the medical existence of oral cancer over times, particularly better comprehending if the apparent lower prevalence of this type of cancer in antiquity is a real value due to the absence of modern environmental and lifestyle factors or it is linked to a misinterpretation of ancient foreign terms found in ancient medical texts regarding oral neoplasms. Methods: The databases MedLne, PubMed, Web of Science, Elsevier’s EMBASE.com, Cochrane Review, National Library of Greece (Stavros Niarchos Foundation, Athens) and the Library of the School of Health Sciences of the National and Kapodistrian University of Athens (Greece) were extensively searched for relevant studies published during the past century on the history of oral cancer and its treatment from antiquity to modern times, in addition to the WHO website to analyse the latest epidemiological data. In addition, we included historical books on the topic of interest and original sources. Results: Historical references reveal that the cradle of the oral oncology was in ancient Egypt, the Asian continent and Greece and cancer management was confined to an approximate surgical practice, in order to remove abnormal masses and avoid bleeding with cauterization. In the Medieval Age, little progress occurred in medicine in general, oral cancers management included. It is only from the Renaissance to modern times that knowledge about its pathophysiological mechanisms and histopathology and its surgical and pharmacological treatment approaches became increasingly deep all over the world, evolving to the actual integrated treatment. Despite the abundant literature exploring oncology in past civilizations, the real prevalence of oral cancer in antiquity is much less known; but a literature analysis cannot exclude a consistent prevalence of this cancer in past populations, probably with a likely lower incidence than today, because many descriptions of its aggressiveness were found in ancient medical texts, but it is still difficult to be sure that each single description of oral masses could be associated to cancer, particularly for what concerns the period before the Middle Ages. Conclusions: Modern oncologists and oral surgeons must learn a lot from their historic counterparts in order to avoid past unsuccessful efforts to treatment oral malignancies. Several descriptions of oral cancers in the antiquity that we found let us think that this disease might be linked to mechanisms not strictly dependent on environmental risk factors, and this might guide future research on oral cavity treatments towards strategical cellular and molecular techniques.

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Targeting tumor-associated macrophages in head and neck squamous cell carcinoma

Cited by 45 publications

References 111 publications

Endoplasmic Reticulum Stress Promotes The Release of Exosomal PD-L1 From Head and Neck Cancer Cells and Facilitates M2 Macrophage Differentiation

Endoplasmic Reticulum Stress Promotes The Release of Exosomal PD-L1 From Head and Neck Cancer Cells and Facilitates M2 Macrophage Differentiation

Animal model and bioinformatics analyses suggest the TIMP1/MMP9 axis as a potential biomarker in oral squamous cell carcinoma

Oral Cancer: A Historical Review

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