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Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Abstract Head and neck squamous cell carcinoma (HNSCC) is among the most severe and complex malignant diseases with a high level of heterogeneity and, as a result, a wide range of therapeutic responses, regardless of clinical stage. Tumor progression depends on ongoing co-evolution and cross-talk with the tumor microenvironment (TME). In particular, cancer-associated fibroblasts (CAFs), embedded in the extracellular matrix (ECM), induce tumor growth and survival by interacting with tumor cells. Origin of CAFs is quite varied, and the activation patterns of CAFs are also heterogeneous. Crucially, the heterogeneity of CAFs appears to play a key role in ongoing tumor expansion, including facilitating proliferation, enhancing angiogenesis and invasion, and promoting therapy resistance, through the production of cytokines, chemokines, and other tumor-promotive molecules in the TME. This review describes the various origin and heterogeneous activation mechanisms of CAFs, and biological heterogeneity of CAFs in HNSCC is also included. Moreover, we have highlighted versatility of CAFs heterogeneity in HNSCC progression, and have discussed different tumor-promotive functions of CAFs respectively. In the future, it is a promising strategy for the therapy of HNSCC that specifically targeting tumor-promoting CAF subsets or the tumor-promoting functional targets of CAFs.

Obtaining accurate basic parameters for long hole blasting is challenging, and the resulting vibration damage significantly impacts key surface facilities. Predicting ground vibration velocity accurately and mitigating the harmful effects of blasting are crucial aspects of controlled blasting technology. This study focuses on the prediction of ground vibration velocity induced by underground long hole blasting tests. Utilizing the fitting equation based on the US Bureau of Mines (USBM) formula as a baseline for predicting peak particle velocity, two machine learning models suitable for small sample data, Support Vector Regression (SVR) machine and Random Forest (RF), were employed. The models were optimized using the particle swarm optimization algorithm (PSO) to predict peak particle velocity with multiple parameters specific to long hole blasting. Mean absolute error (MAE), mean Squared error (MSE), and coefficient of determination (R2) were used to assess the model predictions. Compared with the fitting equation based on the USBM model, both the Support Vector Regression (SVR) and Random Forest (RF) models accurately and effectively predict peak particle velocity, enhancing prediction accuracy and efficiency. The SVR model exhibited slightly superior predictive performance compared to the RF model.

Objectives: To compare the outcomes of tyrosine kinase inhibitors (TKIs) in combination with reduced-dose chemotherapy with those of standard induction chemotherapy, as well as the outcomes between chemotherapy and transplantation, in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).Methods: We retrospectively reviewed cases of Ph+ ALL treated with TKIs and combination chemotherapy. The patients were allocated to either the TKIs with reduced-dose chemotherapy group or the TKIs with standard chemotherapy group. In additions, patients were further stratified into either the transplant group or the non-transplant group.Results: The complete remission rate (88.7% vs. 83.9%, p = 0.372), major molecular response (58.9% vs. 56.0%, p = 0.750), molecular complete response (20.5% vs. 22.0%, p = 0.891), and early mortality rate (3.2% vs. 3.5%, p = 0.922) were similar between the TKIs with reduced-dose chemotherapy group and the TKIs with standard chemotherapy group. The proportions of lung infections, bloodstream infections, patients with >21 days of hospitalization, the total costs, transfusion costs, and antimicrobial costs were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. The 3-year overall survival rates (59.0% [95% CI, 46.6–74.7%] vs. 38.4% [95% CI, 29.9–49.4%]) and disease-free survival rates (48.6% [95% CI, 34.2–69.1%] vs. 32.0% [95% CI, 23.5–43.7%]) were significantly better in the transplant group than in the non-transplant group.Conclusion: An induction regimen combining TKIs with reduced-dose chemotherapy and transplantation during the first complete remission remains a suitable and effective option for patients with Ph+ ALL.

ABSTRACT Senecavirus A (SVA) is a type of nonenveloped single-stranded, positive-sense RNA virus. The VP2 protein is a structural protein that plays an important role in inducing early and late immune responses of the host. However, its antigenic epitopes have not been fully elucidated. Therefore, defining the B epitopes of the VP2 protein is of great importance to revealing its antigenic characterization. In this study, we analyzed B-cell immunodominant epitopes (IDEs) of the VP2 protein from the SVA strain CH/FJ/2017 using the Pepscan approach and a bioinformatics-based computational prediction method. The following four novel IDEs of VP2 were identified: IDE1, 41TKSDPPSSSTDQPTTT56; IDE2, 145PDGKAKSLQELNEEQW160; IDE3, 161VEMSDDYRTGKNMPF175; and IDE4, 267PYFNGLRNRFTTGT280. Most of the IDEs were highly conserved among the different strains. To our knowledge, the VP2 protein is a major protective antigen of SVA that can induce neutralizing antibodies in animals. Here, we analyzed the immunogenicity and neutralization activity of four IDEs of VP2. Consequently, all four IDEs showed good immunogenicity that could elicit specific antibodies in guinea pigs. A neutralization test in vitro showed that the peptide-specific guinea pig antisera of IDE2 could neutralize SVA strain CH/FJ/2017, and IDE2 was identified as a novel potential neutralizing linear epitope. This is the first time VP2 IDEs have been identified by using the Pepscan method and a bioinformatics-based computational prediction method. These results will help elucidate the antigenic epitopes of VP2 and clarify the basis for immune responses against SVA. IMPORTANCE The clinical symptoms and lesions caused by SVA are indistinguishable from those of other vesicular diseases in pigs. SVA has been associated with recent outbreaks of vesicular disease and epidemic transient neonatal losses in several swine-producing countries. Due to the continuing spread of SVA and the lack of commercial vaccines, the development of improved control strategies is urgently needed. The VP2 protein is a crucial antigen on the capsids of SVA particles. Furthermore, the latest research showed that VP2 could be a promising candidate for the development of novel vaccines and diagnostic tools. Hence, a detailed exploration of epitopes in the VP2 protein is necessary. In this study, four novel B-cell IDEs were identified using two different antisera with two different methods. IDE2 was identified as a new neutralizing linear epitope. Our findings will help in the rational design of epitope vaccines and further understanding of the antigenic structure of VP2.

Abstract Background Glottic squamous cell carcinoma (GSCC) is the most prevalent type of laryngeal carcinoma. The value of prophylactic lymph node dissection (LND) in resected GSCC remains controversial. This study aims to quantitatively assess the probability of occult lymph node metastasis (LNM) for GSCC patients and devise individualized postoperative radiotherapy strategies. Methods A total of 1319 patients with GSCC were retrospectively analyzed. Results GSCC patients with T1‐T2 stages showed significantly lower LNM rate than those with T3‐T4 stages. For patients with T3‐T4 GSCC, multivariate logistic analyses indicated that three factors—maximum tumor diameter (MTD) of more than 2.0 cm, relatively low differentiation, and tumor invasive depth of no less than 1.0 cm—were independent risk factors for the existence of LNM. A predictive nomogram was established based on these factors. The accuracy and validity of our model were verified by 0.716 and remained at 0.717 after 1000 bootstrapping. The calibration curve was also plotted and showed a favorable agreement. The patients were stratified into two groups based on their individual LNM risk points. Possible LNM rates for low‐risk and high‐risk subgroups were 4.7% and 25.2%, respectively. Conclusions A new post‐operative strategy selection flow chart was established based on our newly created nomogram which can effectively predict the individualized possibility of occult LNM for GSCC patients. For clinical T3‐4N0 patients in the high‐risk subgroup, prophylactic dose post‐operative radiation therapy is recommended. However, for all those clinically diagnosed as T1‐2N0 stage, regular follow‐up is sufficient in view of the low occult LNM rate. Level of Evidence: 2a

Purpose: To explore the discrepancy in clinicopathological and prognostic features between smoking and alcohol drinking (SA) and non-smoking and non-alcohol drinking (NSNA) patients with laryngeal squamous cell carcinoma (LSCC). Methods: This retrospective study including 1735 patients with LSCC was conducted from January 2005 to December 2010, which were categorized into 4 groups, NSNA group, smoking only group, alcohol-drinking only group, and SA group. We compared overall survival (OS) and disease-free survival (DFS) using the Kaplan–Meier method and indicated clinicopathological features by Cox proportional hazards regression models before and after propensity score matching (PSM). Results: A total of 415 patients (23.92%) were identified as NSNA. The SA group was predominantly patients ≤60 years old (46.63%) while the NSNA group was more older (58.07%). NSNA group was more likely to present at earlier disease stage and more female. No significant difference in OS ( P = .685) and DFS ( P = .976) was found between the 2 groups. In addition to age and recurrence and metastasis being common independent prognostic factors in terms of OS in both groups of patients, NSNA group also exhibited other factors, namely tumor area >3.7 cm 2 and positive resection margin. For DFS, N + stage, tumor size >3.7 cm 2 , and positive resection margin were prognostic features specific to NSNA group. Conclusion: The outcome is similar in LSCC patients with and without SA. NSNA group shows a distinct profile from that found in SA group. Clinicopathological features from NSNA group should be considered for LSCC management.

The discriminative correlation filter (DCF)-based tracking method has shown good accuracy and efficiency in visual tracking. However, the periodic assumption of sample space causes unwanted boundary effects, restricting the tracker’s ability to distinguish between the target and background. Additionally, in the real tracking environment, interference factors such as occlusion, background clutter, and illumination changes cause response aberration and, thus, tracking failure. To address these issues, this work proposed a novel tracking method named the background-suppressed dual-regression correlation filter (BSDCF) for visual tracking. First, we utilize the background-suppressed function to crop out the target features from the global features. In the training step, while introducing the spatial regularity constraint and background response suppression regularization, we construct a dual regression structure to train the target and global filters separately. The aim is to exploit the difference between the output response maps for mutual constraint to highlight the target and suppress the background interference. Furthermore, in the detection step, the global response can be enhanced by a weighted fusion of the target response to further improve the tracking performance in complex scenes. Finally, extensive experiments are conducted on three public benchmarks (including OTB100, TC128, and UAVDT), and the experimental results indicate that the proposed BSDCF tracker achieves tracking performance comparable to many state-of-the-art (SOTA) trackers in a variety of complex situations.

During the production of open-pit mines, the stability of slopes can be affected by various factors such as structural surfaces, production blasting vibrations, and mining areas. In this study, the researchers focused on the slope of the open-pit mine at Yinshan and employed UAV mapping technology to conduct an on-site geological engineering investigation. Information on the yield, trace length, spacing, and density of the structural surface of the south slope was obtained. The researchers also carried out vibration blasting tests in combination with the production blasting activities in the mine to determine the blasting vibration attenuation law and whether the blasting vibration speed met safety specifications. Additionally, numerical simulation methods were used to examine the influence of the mining area on the stability of the current slope and the designed excavation slope. The slope stability was evaluated using the limit equilibrium method, and the researchers separately discussed the influence of self-weight load and self-weight load plus blasting vibration force on the stability of the high slope of the open pit. The results showed the following: (1) The rock mass structural plane in the south slope of the mining area was mainly dominated by a medium-large dip structural plane, and three faults and joint fissures in the investigation area combined to form cutting and sliding surfaces in the rock mass that were prone to collapse and sliding. (2) The maximum blasting vibration speed met safety requirements. (3) There was no large range of plastic zone damage in the entire slope, and the overall stability of the slope was good. (4) The present slope was relatively stable when considering only self-weight stress and the blasting vibration force. However, there was a certain risk of instability in the design of the excavation slope.

Accurate indoor localization estimation has important social and commercial values, such as indoor location services and pedestrian retention times. Acoustic-based methods can achieve high localization accuracies in specific scenarios with special equipment; however, it is a challenge to obtain accurate localization with general equipment in indoor environments. To solve this problem, we propose a novel fusion CHAN and the improved pedestrian dead reckoning (PDR) indoor localization system (CHAN-IPDR-ILS). In this system, we propose a step length estimation method that adds the previous two steps for extracting more accurate information to estimate the current step length. The maximum influence factor is set for the previous two steps to ensure the importance of the current step length. We also propose a heading direction correction method to mitigate the errors in sensor data. Finally, pedestrian localization is achieved using a motion model with acoustic estimation and dynamic improved PDR estimation. In the fusion localization, the threshold and confidence level of the distance between estimation base-acoustic and improved PDR estimation are set to mitigate accidental and cumulative errors. The experiments were performed at trial sites with different users, devices, and scenarios, and experimental results demonstrate that the proposed method can achieve a higher accuracy compared with the state-of-the-art methods. The proposed fusion localization system manages equipment heterogeneity and provides generality and flexibility with different devices and scenarios at a low cost.

Bilateral second branchial cleft fistulae are very rare and usually arise from the incomplete obliteration of the branchial apparatus during the embryonic period. Here, we present the clinical characteristics and surgical treatment of a case with bilateral second branchial cleft fistulae coexisting with bilateral pre-auricular fistulae. A 32-year-old man with complaints of a mucus-like discharge that was occasionally secreted on both sides of his neck at 2 years of age when swallowing or pressing the upper area of the two openings. He underwent surgical treatment. The fistulae tracts were traced ascending to the area adjacent to the internal and external carotid arteries, passing the glossopharyngeal and hypoglossal nerves, and opening into the tonsillar fossa finally. The correct diagnosis and definitive surgical excision should be made by a doctor who is familiar with the history, clinical examination, and anatomic structure of the different types of branchial anomalies.

Summary: Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that high enrichment of Fusobacterium nucleatum (F. nucleatum) in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B (ADH1B) and transforming growth factor β receptor 2 (TGFBR2) expression by activating innate immune signaling, resulting in ethanol metabolism reprogramming to allow F. nucleatum accumulation and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition, further exacerbating the uncontrolled progression and metastasis of LSCC. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, which yields valuable insight into clinical management that may improve the oncologic outcome of patients with LSCC.

Abstract Circular RNAs are abundant endogenous non-coding RNA with no 5′ cap and 3′ polyadenylation tail that modify liner mRNAs and have no terminal structures. Our knowledge of the biogenesis of circular RNAs has been expanded, and circular RNAs were shown to be key regulators of various diseases, especially cancers. Head and neck cancers are the sixth most popular cancers worldwide, and the overall survival rates remain unsatisfactory. Recent studies have indicated that circular RNAs are involved in the tumorigenesis, progression, invasion and chemosensitivity of head and neck cancers and that some circular RNAs could serve as diagnostic and prognostic biomarkers. In this study, we summarize research advances in the regulation of circular RNA biogenesis, their characteristics and functions, the involvement of circular RNAs in the pathophysiology of head and neck cancers and their potential clinical utilization, as well as the likely directions of future studies.

Accurate indoor location information has considerable social and economic value in applications, such as pedestrian heatmapping and indoor navigation. Ultrasonic-based approaches have received significant attention mainly since they have advantages in terms of positioning with temporal correlation. However, it is a great challenge to gain accurate indoor localization due to complex indoor environments such as non-uniform indoor facilities. To address this problem, we propose a fusion localization method in the indoor environment that integrates the localization information of inertial sensors and acoustic signals. Meanwhile, the threshold scheme is used to eliminate outliers during the positioning process. In this paper, the estimated location is fused by the adaptive distance weight for the time difference of arrival (TDOA) estimation and improved pedestrian dead reckoning (PDR) estimation. Three experimental scenes have been developed. The experimental results demonstrate that the proposed method has higher localization accuracy in determining the pedestrian location than the state-of-the-art methods. It resolves the problem of outliers in indoor acoustic signal localization and cumulative errors in inertial sensors. The proposed method achieves better performance in the trade-off between localization accuracy and low cost.

Vision-based quadrotor will be a good carrier for big data. This paper investigates the quadrotor tracking control by designing an adaptive sliding mode controller based on the backstepping technique with the advantages of simplicity in design and ease of application. A sliding mode controller is first developed to ensure fast convergence speed with the desired reference, and then the backstepping technique is used until the desired reference trajectory is achieved and finally the appropriate control laws are obtained. In order to achieve the precise and fast localization of a quadrotor, a popular visual odometry algorithm is applied to gathering good position information required in motion estimation. We employ Kalman filter for sensor data fusion and state estimation. Gazebo is applied by creating a 3D dynamic environment to recreate the complex environment potentially encountered in the real world.

Abstract The microbial communities that inhabit the laryngeal mucosa build stable microenvironments and have the potential to influence the health of the human throat. However, the associations between the microbiota structure and laryngeal carcinoma remain uncertain. Here, we explored this question by comparing the laryngeal microbiota structure in laryngeal cancer patients with that in control subjects with vocal cord polyps through high-throughput pyrosequencing. Overall, the genera Streptococcus, Fusobacterium, and Prevotella were prevalent bacterial populations in the laryngeal niche. Tumor tissue samples and normal tissues adjacent to the tumor sites (NATs) were collected from 31 laryngeal cancer patients, and the bacterial communities in laryngeal cancer patients were compared with control samples from 32 subjects. A comparison of the laryngeal communities in the tumor tissues and the NATs showed higher α-diversity in cancer patients than in control subjects, and the relative abundances of seven bacterial genera differed among the three groups of samples. Furthermore, the relative abundances of ten bacterial genera in laryngeal cancer patients differed substantially from those in control subjects. These findings indicate that the laryngeal microbiota profiles are altered in laryngeal cancer patients, suggesting that a disturbance of the microbiota structure might be relevant to laryngeal cancer.

The effect of rolling temperatures on the interface microstructure and mechanical properties is investigated using 2-mm-thick TA1/Q235B composite sheets, which were prepared after nine passes of hot rolling of explosive welded plates. The results show that the vortex region and the transition layer exist in the interface at the explosive welded plate, while only the transition layer exists in the interface after hot rolling. The transition layer is composed of α-Ti, TiC, Fe, and FeTi, and the thickness increases with the increasing rolling temperature. The microhardness of the explosive welded plate is higher than that of the hot-rolling sheet, and the microhardness of interface are higher than that of matrix metals. The interface shear strength and tensile elongation of the hot-rolled sheet increase with the increasing hot rolling temperature, while the ultimate tensile strength (UTS), yield strength (YS) and Young modulus decrease with the increase of hot rolling temperature. The shear strength of sheets is related to the interfacial compounds, and the tensile strength is mainly affected by the grain morphology of the matrix.

Al–Cu, being a high-strength aluminium alloy, is used to prepared castings which are widely used in the automotive and aerospace industries as lightweight parts. However, corrosion is an issue. The Al–Cu alloys show improved properties when other elements are added to them. One such alloy is Al–4.5Cu–3.5Zn–0.5Mg. In order to improve the corrosion resistance and strength of this Al–4.5Cu–3.5Zn–0.5Mg cast alloy, a novel non-isothermal ageing (NIA) treatment was developed that comprised a heating stage up to 250 °C, followed by a cooling stage down to room temperature at the rate of 60 °C·h ^−1 . Specimens were removed throughout the process and immediately quenched for morphological, mechanical, and electrochemical testing. The hardness continuously increased up to 124 HV with ageing time. The alloy exhibited optimal properties after ageing for ~340 min (with the aging temperature reaching 130 °C during the cooling stage of the NIA treatment), with a tensile strength and maximum corrosion depth of 395 MPa and 165 μ m, respectively. Fine precipitates discontinuously appeared at the grain boundaries during the cooling stage. Some new fine Ω phases were precipitated in the grains, thereby narrowing the precipitation-free zone. Thus, high strength and good corrosion resistance of the alloy can be obtained via the NIA treatment. Notably, NIA treatments are less time-consuming than isothermal ageing treatments, thereby expanding the applications of high-strength cast aluminium alloys in the manufacturing industry.

The 1.5 mm thick Cu/Al composite sheet was obtained after explosive-welding and 6 passes cold rolling. The effects of annealing temperature and time on the microstructure, mechanical properties, and conductivity of cold-rolled Cu/Al composite sheets were investigated. The results show that the thickness of the interface diffusion layer with compounds of Al _2 Cu, AlCu, and Al _4 Cu _9 increases with the increase in annealing temperature and holding time, and the total activation energy is 108 kJ mol ^−1 . The tensile strength of composite sheets decreases and the fracture elongation increases with the increase of annealing temperature. Especially when the annealing temperature increased from 300 ℃ to 350 ℃, the tensile yield strength decreased from 225 MPa to 77 MPa, and the elongation increased from 16% to 37.5%. The tensile-shear strength of composite sheets reaches to 117 MPa after annealing at 400 ℃ for 2 h. The conductivity of composite sheet is greatly affected by the annealing time. At the annealing temperature of 350 ℃ and time of 4 h, the composite sheets show a better conductivity of 96.4% IACS.

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti–chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.