[Research Progress on the Interaction Between Microorganisms and Macrophages and Their Role in the Mediation of the Onset and Development of Oral Cancer].

Oral squamous cell carcinoma is the sixth most common malignant tumor in the world, and the clinical treatment effect is not satisfactory. Because of the special nature of its location, oral cancer is inextricably linked with a wide variety of microorganisms, and its pathogenesis and development are also extremely susceptible to microbial regulation. In addition, the mediating role of the immune system is also indispensable to the course of tumor pathogenesis and development, especially tumor-associated macrophages, which amplify the regulatory role of microorganisms, and in turn regulate the microbial population components--two complementary effects that jointly exacerbate oral cancer. Herein, we summarized the existing research on the relationship between microorganisms and macrophages, as well as the regulatory role of microorganisms and macrophages in the pathogenesis and development of oral cancer. We also discussed the current status of and gaps in research on the relationship between microorganisms and macrophages and oral cancer. Both microorganisms and macrophages are considered promising indicators for prognosis, showing potentials to be used as new therapeutic targets. Despite some research interest in the role of microorganisms and macrophages in oral cancer, very few studies have linked them to oral precancerous lesions, and the mutual regulatory relationship between microorganisms and macrophages remains unclear. Therefore, in-depth exploration of the relationship network of microorganisms, macrophages and oral cancer is expected to provide more possibilities for the early diagnosis and treatment of tumors.

Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice.

OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage. METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1ß, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

Evaluation of Novel Anticaries Adhesive in a Secondary Caries Animal Model.

We investigated the anticaries properties of an adhesive containing dimethylaminododecyl methacrylate (DMADDM) in vivo via a secondary caries animal model. Cavities were prepared in the maxillary first molars of Wistar rats. DMADDM-containing adhesives were applied on one side and commercial adhesives on the opposite side as a control. After a 3-week feeding period to induce secondary caries, the molars were harvested for the evaluation of the secondary caries. Lesion depth (LD) and mineral loss (ML) were measured via a micro-CT method, and a modified Keyes scoring method yielded scores for the caries lesions. Statistical analysis was divided into 2 parts: a correlation analysis between 2 evaluations with one-way ANOVA and a least-significant differences (LSD) test, and an evaluation of anticaries adhesives with a paired samples t test. The results showed that: (1) secondary caries was successfully produced in rats; (2) there was a correlation between the modified Keyes scoring method and micro-CT in the evaluation of the secondary caries; (3) the adhesive containing DMADDM significantly reduced both LD and ML (according to micro-CT), and also lowered the scores (based on the modified Keyes scoring method). This suggests that the novel DMADDM adhesive could perform an anticaries function in vivo via the secondary caries animal model which was also developed and testified in research. Secondary caries is one of the major reasons leading to the failure of caries restoration treatment. As a solution, anticaries adhesives perform well in biofilm inhibition in vitro. However, the lack of secondary caries animal models limits the evaluation of anticaries adhesives in vivo.

Anti-Bacteria and Microecosystem-Regulating Effects of Dental Implant Coated with Dimethylaminododecyl Methacrylate.

The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, respectively. Biomass accumulation and metabolic activity of biofilms were tested using crystal violet assay and MTT (3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 16S rRNA gene sequencing was performed to measure the microbial community. Live/dead staining and scanning electron microscopy (SEM) were used to value the structure of biofilm. The results showed that the higher mass fraction of DMADDM the coating solution had, the significantly lower the values of metabolic activity and accumulated biofilms got, as well as fewer live cells and less extracellular matrix. Moreover, 5 mg/mL of DMADDM was the most effective concentration, as well as 10 mg/mL. In microecosystem-regulation, the DMADDM modified titanium implant decreased the relative abundance of Neisseria and Actinomyces and increased the relative abundance of Lactobacillus, a probiotic for peri-implant diseases. In conclusion, via inhibiting growth and regulating microecosystem of biofilm, this novel titanium implant coating with DMADDM was promising in preventing peri-implant disease in an 'ecological manner'.

Effect of Antimicrobial Denture Base Resin on Multi-Species Biofilm Formation.

Our aims of the research were to study the antimicrobial effect of dimethylaminododecyl methacrylate (DMADDM) modified denture base resin on multi-species biofilms and the biocompatibility of this modified dental material. Candida albicans (C. albicans), Streptococcus mutans (S. mutans), Streptococcus sanguinis (S. sanguinis), as well as Actinomyces naeslundii (A. naeslundii) were used for biofilm formation on denture base resin. Colony forming unit (CFU) counts, microbial viability staining, and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) array were used to evaluate the antimicrobial effect of DMADDM. C. albicans staining and Real-time PCR were used to analyze the morphology and expression of virulence genes of C. albicans in biofilm. Lactate dehydrogenase (LDH) array and Real-time PCR were conducted to examine the results after biofilm co-cultured with epithelial cell. Hematoxylin and eosin (HE) staining followed by histological evaluation were used to study the biocompatibility of this modified material. We found that DMADDM containing groups reduced both biomass and metabolic activity of the biofilm significantly. DMADDM can also inhibit the virulence of C. albicans by means of inhibiting the hyphal development and downregulation of two virulence related genes. DMADDM significantly reduced the cell damage caused by multi-species biofilm according to the LDH activity and reduced the expression of IL-18 gene of the cells simultaneously. The in vivo histological evaluation proved that the addition of DMADDM less than 6.6% in denture material did not increase the inflammatory response (p > 0.05). Therefore, we proposed that the novel denture base resin containing DMADDM may be considered as a new promising therapeutic system against problems caused by microbes on denture base such as denture stomatitis.

Effects of the adjunctive therapy of Sun's abdominal acupuncture on acute ischemic stroke and inflammatory factors: a randomized controlled trial. / å­™æ°è ¹é’ˆè¾ åŠ©æ²»ç–—æ€¥æ€§è„‘æ¢—æ­»åŠå¯¹ç‚Žæ€§å› å­çš„å½±å“ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the clinical effect on acute ischemic stroke (AIS) between the combined treatment of Sun's abdominal acupuncture combined with the routine acupuncture and the simple routine acupuncture, and explore the influences on inflammatory factors i.e. interleukin (IL)-1ß and IL-10. METHODS: Eighty patients with AIS were randomly divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case dropped out). The routine regimens of western medicine were administered in the two groups. In addition, the routine scalp acupuncture and the body acupuncture were used in the patients of the control group. The scalp acupuncture stimulation region and acupoints included the anterior parietal-temporal oblique line, Hegu (LI 4), Chize (LU 5), Shousanli (LI 10), etc. of affected side. In the observation group, on the base of the intervention of the control group, electroacupuncture was applied to "fouth abdominal area" of Sun's abdominal acupuncture, with the continuous wave and the frequency of 5 Hz. In the two groups, the intervention was given twice per day, once in every morning and afternoon separately, with the needles retained for 40 min in each intervention. The interventions were delivered for 6 days a week, lasting 3 weeks. The scores of Fugl-Meyer assessment scale (FMA), Berg balance scale (BBS) and the modified Barthel index (MBI), and the levels of IL-1ß and IL-10 in the serum were observed before and after treatment in the two groups; the effect and safety of interventions were compared between the two groups. RESULTS: After treatment, the scores of FMA, BBS and MBI increased in comparison with those before treatment in the two groups (P<0.01), and these scores in the observation group were higher than those in the control group (P<0.05, P<0.01). After treatment, in the two groups, the levels of IL-1ß in the serum were reduced in comparison with those before treatment (P<0.01), and the IL-1ß level in the observation group was lower than that in the control group (P<0.05); the levels of IL-10 in the serum were elevated in comparison with those before treatment in the two groups (P<0.01) and the IL-10 level in the observation group was higher than that in the control group (P<0.05). The total effective rate was 92.3% (36/39) in the observation group, which was superior to that in the control group (84.6% [33/39], P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS: Sun's abdominal acupuncture combined with the routine acupuncture can ameliorate the motor impairment, adjust the balance dysfunction and improve the activities of daily living in the patients with AIS. The therapeutic effect of this combined regimen is better than that of the routine acupuncture, which may be associated with the regulation of the inflammatory factors after cerebral infarction.

CD47-SIRPα Blockade Sensitizes Head and Neck Squamous Cell Carcinoma to Cetuximab by Enhancing Macrophage Adhesion to Cancer Cells.

Developing effective treatments for patients with head and neck squamous cell carcinoma (HNSCC) is a significant challenge. Cetuximab, a first-line targeted therapy for HNSCC, exhibits limited efficacy. Here, we used pooled CRISPR screening to find targets that can synergize with cetuximab and identified CD47 as the leading candidate. Rather than inhibiting cancer cell proliferation, CD47 inhibition promoted cetuximab-triggered antibody-dependent cellular phagocytosis (ADCP), thereby enhancing macrophage-mediated cancer cell removal. The combination of CD47-signal-regulatory protein α (SIRPα) blockade and cetuximab demonstrated strong anticancer activity in vivo. In addition to blocking the phagocytosis checkpoint, CD47-SIRPα inhibition upregulated CD11b/CD18 on the surface of macrophages, which accelerated intercellular adhesion between macrophages and cancer cells to enhance subsequent phagocytosis. Inhibition of the interaction between macrophage CD11b/CD18 and cancer cell intercellular adhesion molecule-1 (ICAM1) eliminated the intercellular adhesion and phagocytosis induced by CD47-SIRPα blockade. Thus, CD47-SIRPα blockade enhances ADCP through CD11b/CD18-ICAM1-mediated intercellular adhesion and sensitizes HNSCC to cetuximab. Significance: CD47-SIRPα blockade increases surface CD11b/CD18 on macrophages to enhance adhesion to cancer cells, resulting in robust synergistic phagocytosis in combination with cetuximab treatment in head and neck squamous cell carcinoma.

Dodecylmethylaminoethyl methacrylate inhibits Enterococcus faecalis in a pH-dependent manner.

OBJECTIVES: Considering the correlation between survival microenvironment of E. faecalis and acidic pH value, this study aimed to investigate the potential of utilizing pH-responsive DMAEM monomers and their copolymers with resin-based root canal sealers to inhibit E. faecalis. METHODS: Broth microdilution assay, crystal violet staining and qPCR were performed to evaluate antibacterial effects of DMAEM monomers against E. faecalis at different pH. Methacrylate-resin based root canal sealers were prepared and copolymerized with DMAEM. The flow, solubility, water sorption, apical sealing ability and cytotoxicity of sealers were investigated to optimize formulation. The anti-E. faecalis effects of DMAEM copolymers with sealers were evaluated by direct contact test, colony-forming unit counting and live/dead staining. RESULTS: DMAEM monomers inhibited the growth, biofilm formation and virulence factors expression of E. faecalis in a concentration- and pH-dependent manner. Incorporation of 1.25 % and 2.5 % DMAEM into experimental sealers would not affect the flowability, solubility and periapical sealing ability (P > 0.05), but increased the water sorption of sealers (P < 0.01). Cells viability was higher than 90 % in both 1.25 % and 2.5 % DMAEM groups at pH 7.0. DMAEM copolymers with sealers reduced E. faecalis counts, inhibited biofilm formation and decreased live cells within the biofilm in response to pH values. SIGNIFICANCE: DMAEM monomers and their copolymers with resin-based sealers possessed antibacterial and antibiofilm effects on E. faecalis in response to pH values. DMAEM is promising to inhibit intraradicular E. faecalis in response to its acidic survival environment and maintain low cytotoxicity under neutral conditions, ensuring their biosafety in case of inadvertent entry into periapical tissues.

A novel pH-responsive monomer inhibits Candida albicans via a dual antifungal mode of action.

The scarcity of the antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived CC double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, the tertiary amine of DMAEM protonates into a cationic fungicide, sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting the CHK1 two-component system in C. albicans. At neutral pH, the methacrylate-derived CC double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering the extracellular vesicles of C. albicans. These findings support that the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.

The interaction between innate immunity and oral microbiota in oral diseases.

INTRODUCTION: Innate immunity serves as the frontline to combat invading pathogens. Oral microbiota is the total collection of microorganisms colonized within the oral cavity. By recognizing the resident microorganisms through pattern recognition receptors, innate immunity is capable of interacting with oral microbiota and maintaining homeostasis. Dysregulation of interaction may lead to the pathogenesis of several oral diseases. Decoding the crosstalk between oral microbiota and innate immunity may be contributory to developing novel therapies for preventing and treating oral diseases. AREAS COVERED: This article reviewed pattern recognition receptors in the recognition of oral microbiota, the reciprocal interaction between innate immunity and oral microbiota, and discussed how the dysregulation of this relationship leads to the pathogenesis and development of oral diseases. EXPERT OPINION: Many studies have been conducted to illustrate the relationship between oral microbiota and innate immunity and its role in the occurrence of different oral diseases. The impact and mechanisms of innate immune cells on oral microbiota and the mechanisms of dysbiotic microbiota in altering innate immunity are still needed to be investigated. Altering the oral microbiota might be a possible solution for treating and preventing oral diseases.

Applications of quaternary ammonium compounds in the prevention and treatment of oral diseases: State-of-the-art and future directions.

OBJECTIVES: The aim of this review is to comprehensively summarize the state-of-the-art developments of quaternary ammonium compounds (QACs) in the prevention and treatment of oral diseases. By discussing the structural diversity and the potential killing mechanism, we try to offer some insights for the future research of QACs. DATA, SOURCES & STUDY SELECTION: A literature search was conducted in electronic databases (Web of Science, PubMed, Medline, and Scopus). Publications that involved the applications of QACs, especially those related to the prevention and treatment of oral diseases, are included. RESULTS: We have reviewed the relevant research on QACs over the past two decades. The research results indicate that the current applications are mainly focused on dental material modification and direct pharmacological interventions. Concurrently, challenges such as potential risks to normal tissues and impediments in drug resistance and microbial persistence present certain application constraints. The latest studies have encompassed the exploration of smart materials and nanoparticle formulations. CONCLUSIONS: The killing mechanism may possess a threshold related to charge density. However, the exact process remains enigmatic. The structural diversity and the exploration of intelligent materials and nanoparticle formulations provide directions in development of novel QACs. CLINICAL SIGNIFICANCE: The intricate oral anatomy, combined with the multifaceted oral microbiome, necessitates specialized materials for the targeted prevention and treatment of oral pathologies. QACs represent a cohort of compounds distinguished by potent anti-infective and anti-tumor attributes. Innovations in intelligent materials and nanoparticle formulations amplify their potential in significantly advancing the prevention and therapeutic interventions for oral diseases.

The CD47-SIRPα axis is a promising target for cancer immunotherapies.

Cluster of differentiation 47(CD47) is a transmembrane protein that is ubiquitously found on the surface of many cells in the body and uniquely overexpressed by both solid and hematologic malignant cells. CD47 interacts with signal-regulatory protein α (SIRPα), to trigger a "don't eat me" signal and thereby achieve cancer immune escape by inhibiting macrophage-mediated phagocytosis. Thus, blocking the CD47-SIRPα phagocytosis checkpoint, for release of the innate immune system, is a current research focus. Indeed, targeting the CD47-SIRPα axis as a cancer immunotherapy has shown promising efficacies in pre-clinical outcomes. Here, we first reviewed the origin, structure, and function of the CD47-SIRPα axis. Then, we reviewed its role as a target for cancer immunotherapies, as well as the factors regulating CD47-SIRPα axis-based immunotherapies. We specifically focused on the mechanism and progress of CD47-SIRPα axis-based immunotherapies and their combination with other treatment strategies. Finally, we discussed the challenges and directions for future research and identified potential CD47-SIRPα axis-based therapies that are suitable for clinical application.

Challenges and Opportunities for Dental Education from COVID-19.

With the ongoing COVID-19 pandemic, dental education has been profoundly affected by this crisis. First of all, COVID-19 brought physical and psychological health problems to dental students and educators. In addition, both non-clinical teaching and clinical-based training experienced challenges, ranging from fully online educational content to limited dental training, students' research was delayed in achieving project milestones and there was hesitancy in respect of the COVID-19 vaccine. On the other hand, the COVID-19 pandemic has increased the demand for teledentistry and dental emergency treatment, and brought awareness of the advantages and high-speed development of distance education. This review aims to present these challenges and opportunities for dental education, and suggest how dental institutions should prepare for the future demand for dental education.

Effect of the Modified Methacrylate-Based Root Canal Sealer in Single-Cone Technique.

This study aimed to modify EndoREZ with 2.5% dimethylaminododecyl methacrylate (DMADDM) and 1% magnetic nanoparticles (MNP) to study its sealing property, penetration and long-term antibacterial and therapeutic effect in the single-cone technique (SCT) compared with EndoREZ and iRoot SP. Thirty single-root human maxillary premolars were assigned into three groups and obturated with three different root canal sealers by SCT. Every specimen was then scanned using micro-CT to analyze void fraction, and void volumes and confocal laser scanning microscope (CLSM) was used to study the dentin penetration. The long-term antimicrobial effects were tested in vitro before and after aging 1 and 4 weeks by the single-strain Enterococcus faecalis biofilm model. In addition, the beagle canine model of apical periodontitis (AP) was utilized to judge and compare the therapeutic effect of three sealers in SCT. The void fraction and void volumes of the modified root canal sealer were not significantly different from iRoot SP (p > 0.05) but were lower than EndoREZ (p < 0.05). The modified root canal sealant displayed a greater penetration, long-term antibacterial property, and treatment effect than the other groups (p < 0.05). This indicated that after being modified with DMADDM and MNP, it showed better performance in SCT.

Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy.

Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy. We identified paclitaxel as a universal adjuvant that efficiently potentiated ADCP by a variety of anticancer antibodies in multiple cancers. Rather than eliciting cytotoxicity on cancer cells, paclitaxel polarized macrophages toward a state with enhanced phagocytic ability. Paclitaxel-treated macrophages down-regulated cell surface CSF1R whose expression was negatively correlated with patient survival in multiple malignancies. The suppression of CSF1R in macrophages enhanced ADCP of cancer cells, suggesting a role of CSF1R in regulating macrophage phagocytic ability. Together, these findings define a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and promote the therapeutic efficacy of clinical anticancer antibodies.

Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy.

The past two decades witnessed a revolution in our understanding of host-microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.

Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer.

BACKGROUND: Limited therapeutic options are available for triple-negative breast cancer (TNBC), emphasizing an urgent need for more effective treatment approaches. The development of strategies by targeting tumor-associated macrophages (TAMs) to stimulate their ability of Programmed Cell Removal (PrCR) provides a promising new immunotherapy for TNBC treatment. METHODS: CD47 is a critical self-protective "don't eat me" signal on multiple human cancers against macrophage immunosurveillance. Using human and mouse TNBC preclinical models, we evaluated the efficacy of PrCR-based immunotherapy by blocking CD47. We performed high-throughput screens on FDA-approved anti-cancer small molecule compounds for agents potentiating PrCR and enhancing the efficacy of CD47-targeted therapy for TNBC treatment. RESULTS: We showed that CD47 was widely expressed on TNBC cells and TAMs represented the most abundant immune cell population in TNBC tumors. Blockade of CD47 enabled PrCR of TNBC cells, but the efficacy was not satisfactory. Our high-throughput screens identified cabazitaxel in enhancing PrCR-based immunotherapy. A combination of CD47 blockade and cabazitaxel treatment yielded a highly effective treatment strategy, promoting PrCR of TNBC cells and inhibiting tumor development and metastasis in preclinical models. We demonstrated that cabazitaxel potentiated PrCR by activating macrophages, independent of its cytotoxicity toward cancer cells. When treated with cabazitaxel, the molecular and phenotypic signatures of macrophages were polarized toward M1 state, and the NF-kB signaling pathway became activated. CONCLUSION: The combination of CD47 blockade and macrophage activation by cabazitaxel synergizes to vastly enhance the elimination of TNBC cells. Our results show that targeting macrophages is a promising and effective strategy for TNBC treatment.

The Clinical Potential of Oral Microbiota as a Screening Tool for Oral Squamous Cell Carcinomas.

Introduction: The oral squamous cell carcinoma (OSCC) is detrimental to patients' physical and mental health. The prognosis of OSCC depends on the early diagnosis of OSCC in large populations. Objectives: Here, the present study aimed to develop an early diagnostic model based on the relationship between OSCC and oral microbiota. Methods: Overall, 164 samples were collected from 47 OSCC patients and 48 healthy individuals as controls, including saliva, subgingival plaque, the tumor surface, the control side (healthy mucosa), and tumor tissue. Based on 16S rDNA sequencing, data from all the five sites, and salivary samples only, two machine learning models were developed to diagnose OSCC. Results: The average diagnostic accuracy rates of five sites and saliva were 98.17% and 95.70%, respectively. Cross-validations showed estimated external prediction accuracies of 96.67% and 93.58%, respectively. The false-negative rate was 0%. Besides, it was shown that OSCC could be diagnosed on any one of the five sites. In this model, Actinobacteria, Fusobacterium, Moraxella, Bacillus, and Veillonella species exhibited strong correlations with OSCC. Conclusion: This study provided a noninvasive and inexpensive way to diagnose malignancy based on oral microbiota without radiation. Applying machine learning methods in microbiota data to diagnose OSCC constitutes an example of a microbial assistant diagnostic model for other malignancies.

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

In head and neck squamous cell carcinoma (HNSCC), tumor-associated macrophages (TAMs) are associated with a poorer prognosis. TAMs, derived from inflammatory monocyte, play a critical role in regulating tumor progression. Generally, TAMs promote tumor progression and suppress immune response via both innate and adaptive immune mechanisms. However, as the double-blade sword, TAMs retain the potential pro-inflammatory ability to inhibit tumor progression. 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 are entering the clinical arena. In this review, we discuss the immunosuppressive role of TAMs in the tumor microenvironment and the therapeutic approaches targeting macrophages which offer promise in improving HNSCC outcome.

Warburg Effect Is a Cancer Immune Evasion Mechanism Against Macrophage Immunosurveillance.

Evasion of immunosurveillance is critical for cancer initiation and development. The expression of "don't eat me" signals protects cancer cells from being phagocytosed by macrophages, and the blockade of such signals demonstrates therapeutic potential by restoring the susceptibility of cancer cells to macrophage-mediated phagocytosis. However, whether additional self-protective mechanisms play a role against macrophage surveillance remains unexplored. Here, we derived a macrophage-resistant cancer model from cells deficient in the expression of CD47, a major "don't eat me" signal, via a macrophage selection assay. Comparative studies performed between the parental and resistant cells identified self-protective traits independent of CD47, which were examined with both pharmacological or genetic approaches in in vitro phagocytosis assays and in vivo tumor models for their roles in protecting against macrophage surveillance. Here we demonstrated that extracellular acidification resulting from glycolysis in cancer cells protected them against macrophage-mediated phagocytosis. The acidic tumor microenvironment resulted in direct inhibition of macrophage phagocytic ability and recruitment of weakly phagocytic macrophages. Targeting V-ATPase which transports excessive protons in cancer cells to acidify extracellular medium elicited a pro-phagocytic microenvironment with an increased ratio of M1-/M2-like macrophage populations, therefore inhibiting tumor development and metastasis. In addition, blockade of extracellular acidification enhanced cell surface exposure of CD71, targeting which by antibodies promoted cancer cell phagocytosis. Our results reveal that extracellular acidification due to the Warburg effect confers immune evasion ability on cancer cells. This previously unrecognized role highlights the components mediating the Warburg effect as potential targets for new immunotherapy harnessing the tumoricidal capabilities of macrophages.