NAD+ metabolism reprogramming mediated irradiation-induced immunosuppressive polarization of macrophages.

PURPOSE: radiotherapy stands as an important complementary treatment for head and neck squamous cell carcinoma (HNSCC), yet it does not invariably result in complete tumor regression. The infiltration of immunosuppressive macrophages is believed to mediate the radiotherapy resistance, which mechanism remains largely unexplored. This study aimed to elucidate the role of immunosuppressive macrophages during radiotherapy and the associated underlying mechanisms. MATERIALS AND METHODS: Male C3H mice bearing syngeneic SCC-VII tumor were received irradiation (2 × 8Gy). The impact of irradiation on tumor-infiltrating macrophages were assessed. Bone marrow derived macrophages were evaluated in differentiation, proliferation, migration, and inflammatory cytokines after treatment of irradiated tumor culture medium (irCM) and irradiated tumor derived extracellular vesicles (irTEVs). A comprehensive metabolomics profiling of the irTEVs was conducted using liquid chromatography-mass spectrometry, while key metabolites were investigated the mechanism in macrophage in vitro and in vivo. RESULTS: Radiotherapy on SCC-VII syngeneic graft tumors increased polarization of both M1 and M2 macrophages in tumor microenvironment and drove infiltrated macrophages towards an immunosuppressive phenotype. Irradiation-induced polarization and immunosuppression of macrophages were dependent on irTEVs which delivered an increased amount of nicotinamide (NAM) to macrophages. NAM directly bound to the NF-κB transcriptional activity regulator USP7, through which NAM reduced translocation of NF-κB into the nucleus, thereby decreasing the release of cytokines IL6 and IL8. Increased enzyme activity of nicotinamide phosphoribosyl transferase (NAMPT) which is the rate-limiting enzyme of NAD+ metabolism, contributed to the irradiation-induced accumulation levels of NAM in irradiated HNSCC and irTEVs. Inhibition of NAMPT decreased NAM levels in irTEVs and increased radiotherapy sensitivity through alleviating immunosuppressive function of macrophages. CONCLUSIONS: Radiotherapy could induce NAD+ metabolic reprogramming of HNSCC cells, which regulate macrophage towards an immunosuppressive phenotype. Pharmacological targeting NAD+ metabolism might be a promising strategy for radiotherapy sensitization of HNSCC.

Segmental mandibulectomy and microvascular reconstruction with fibula free flap: Comparison between intraoral and extraoral approaches.

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.

Diagnosis and Treatment of an Unusual Maxillary Gingiva Malignant Melanoma Arising Around Dental Implant.

BACKGROUND: Oral mucosal malignant melanoma (OMMM) arises from malignant melanocytes, and the most affected age, sex, and site are 20 to 83 years, male, and the mucosa of hard palate and maxillary gingiva, respectively. Despite several cases of OMMM have been published in the literature, cases of malignant melanoma arising around the dental implant are rarely reported. CASE SUMMARY: A 59-year-old male was admitted to our Department with the complain of gingival black pigmentations following dental implant treatment for 3 years. Intraoral examination revealed a painless black lobulated mass around maxillary gingiva and alveolar fossa of dental implant (first molar). CBCT revealed bone destruction around the implant. Positron emission tomography/computed tomography confirmed the presence of tumoral lesion, which was diagnosed as right maxillary gingiva malignant melanoma (T4aN0M0). Partial maxillectomy+buccal fat pad transfer+free tissue patch repair were carried out. Pathologic analyses confirmed the diagnosis of malignant melanoma. The postoperative course was uneventfully, the patient is undergoing follow-up without any evidence of recurrence. CONCLUSION: Our report showed that an ill-fitting dental implant may cause OMMM. Excisional biopsy with sufficient surgical margins allows complete removal and final diagnosis of OMMM. Early diagnosis and treatment are recommended.

Endoscopic Neck Dissection and Intraoral Approach for Oral Cancer and Free Flap Reconstruction.

This study aimed to report our experience about endoscopic neck dissection through a post-auricular hairline incision, followed by intraoral resection of oral cancer and free flap reconstruction. Laryngoscope, 2024.

Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models.

Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Dysregulation of peripheral and intratumoral KLRG1+ CD8+T cells is associated with immune evasion in patients with non-small-cell lung cancer.

OBJECTIVES: Killer cell lectin like receptor G1 (KLRG1) is identified as a co-inhibitory receptor for NK cells and antigen-experienced T cells. The role of KLRG1 in immune regulation in patients with non-small cell lung cancer (NSCLC) remains poorly understood. MATERIALS AND METHODS: We measured the proportion and immune function of KLRG1+CD8+T cells derived from peripheral blood in patients with NSCLC by flow cytometry. Besides, using data from the gene expression profiles and single-cell sequencing, we explored the expression and immune role of KLRG1 in tumor tissues of patients with NSCLC. We further determined the prognostic value of KLRG1 in terms of overall survival (OS) in NSCLC patients. RESULTS: We found that the proportion of KLRG1+CD8+T cells in peripheral blood significantly increased in patients with NSCLC as compared to those with benign pulmonary nodules and healthy donors. Peripheral KLRG1+CD8+T cell proportion was increased in elder subjects compared to that in younger ones, implying an immunosenescence phenotype. Moreover, the KLRG1+CD8+T cell levels were positively correlated with tumor size and TNM stage in the NSCLC cohort. In vitro stimulation experiments demonstrated that the KLRG1+CD8+T cells from peripheral blood expressed higher levels of Granzyme B and perforin than the KLRG1-CD8+ T cells. However, single-cell RNA sequencing data revealed that the KLRG1+CD8+ T cells were less infiltrated in tumor microenvironment and exhibited impaired cytotoxicity. The KLRG1 gene expression levels were significantly lower in tumor tissues than that in normal lung tissues, and were inversely correlated with CDH1 expression levels. Moreover, higher expression of CDH1 in tumor tissues predicted worse overall survival only in patients with KLRG1-high expression, but not in the KLRG1-low subset. CONCLUSION: This study demonstrates that KLRG1+CD8+T cells were associated with tumor immune evasion in NSCLC and suggests KLRG1 as a potential immunotherapy target.

Chinese surgical robot-assisted surgery for parotid tumor: a case report.

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.

Vascularized fascial flap for reconstruction of combined oral mucosa-mandibular defects: The multi-modal biological assessment.

OBJECTIVE: The reconstruction of composite defects in the oral and maxillofacial region using vascularized fascial flaps, such as the fibular, iliac, and temporal fascial flaps, has gained increasing attention among surgeons. However, there remains uncertainty regarding the suitability of fascial flaps as transplants, as well as their healing processes and outcomes, due to their non-mucosal nature. This study aims to comprehensively assess the biological aspects of vascularized fascial flaps at clinical, histological, and genetic levels, with the goal of providing essential biological references for their clinical application. STUDY DESIGN: This study enrolled three patients who underwent reconstruction of combined oral mucosa-mandibular defects using fibular vascularized fascial flaps between 2020 and 2023. Data regarding changes in the appearance of the fascial flaps, bulk-RNA sequencing, and histological slices of initial fascia, initial gingiva, and transformed fascia were collected and analyzed. RESULTS: Within three months, the fascial flaps exhibited rapid epithelial coverage and displayed distinct characteristics resembling mucosa. High-throughput RNA sequencing analyses and histological slices revealed that the transformed fascia exhibited tissue structures similar to mucosa and demonstrated unique advantages in promoting blood vessel formation and reducing scarring through the high-level expression of relevant genes. CONCLUSION: These findings emphasize the potential and feasibility of utilizing vascularized fascial flaps for oral mucosa reconstruction, establishing their unique advantage as transplant materials, and providing significant biological information and references for their selection and clinical application.

Innovative principle of implant-oriented fibula placement in mandibular reconstruction using double-barrel fibula and simultaneous implants: A technical note.

Simultaneous or secondary inserted implants with double-barrel fibula to reconstruct the mandible have become a common method. However, difficulties in later restoration caused by placement errors of fibula or incipiently placed implants have also been reported in some studies. This note describes a novel technique of implant-oriented guide plates helpful for mandible ablation, fibula segmentation and positioning, and implant placement. We design a series of guide plates especially an implant-fibula placing guide plate, and record and fix the relative spatial positions of the remaining teeth, the simultaneous implants and upper fibula. During surgery, the placement of upper fibula is oriented towards appropriate placement of implants. Therefore, the position of upper fibula can meet the requirements of simultaneous implant as much as possible. Within the limits of present observation, we believe that this technique may increase the manipuility while reducing the errors and the risk of complications.

Tumor-infiltrating immune cell score as an independent prognostic predictor for endometrial carcinoma: Insights from a comprehensive analysis of the immune landscape.

BACKGROUND: Immune cells are crucial components in the tumor microenvironment and have a significant impact on the outcomes of patients. AIMS: Here, we aimed to establish a prognostic score based on different types of tumor-infiltrating immune cells for Endometrial Carcinoma (EC). METHODS AND RESULTS: We enrolled and analyzed 516 EC patients from The Cancer Genome Atlas. The relative abundance of 22 immune cells were estimated by using the CIBERSORTx algorithm. Cox regression was performed to identify potential prognostic immune cells, which were used to develop a Tumor-infiltrating Immune Cell Score (TICS). The prognostic and incremental value of TICS for overall survival were compared with traditional prognostic factors using the C-index and decision curves. Clustering analysis using all immune cells identified three immune landscape subtypes, which had weak correlation with survival. A TICS was constructed using CD8T cells, resting memory CD4 T cells, activated NK and activated DCs, and classified patients as low-, moderate- and high-risk subgroups. The low-risk subgroup had higher tumor mutation burden and activation of IL2/STAT5, IL2/STAT3 and IFN-gamma response pathways. Conversely, the high-risk subgroup was associated with DNA copy number variation, hypoxia and EMT process. The TICS subgroups significantly predicted overall survival, which was independent of patient age, tumor stage, grade and molecular classification. Moreover, we developed a nomogram incorporating TICS and clinicopathologic factors, which significantly improved the predictive accuracy compared to the clinicopathologic model alone. CONCLUSION: The TICS is an effective and independent prognostic predictor for EC patients and may serve as a useful supplement to clinicopathological factors and molecular subtyping.

Carcinosarcoma of the deep lobe of the parotid gland in the parapharyngeal region: A case report.

BACKGROUND: Salivary carcinosarcoma is an extremely rare tumor containing both malignant epithelial and mesenchymal constituents. This article reports a rare case of carcinosarcoma with salivary duct carcinoma and osteosarcoma as the tumor components. The clinicopathological characteristics, treatment, and prognosis are discussed in conjunction with the literature. CASE SUMMARY: A 48-year-old man presented with a complaint of a mass in the right parotid region. Osteosarcoma was first considered for assessment by fine-needle aspiration cytology. Physical examination revealed a mass measuring approximately 4 cm × 3.5 cm × 3 cm. The mass, the whole lobe of the right parotid gland, and the right mandible were completely removed during surgery. Postoperative histopathology confirmed carcinosarcoma of the salivary gland. CONCLUSION: A definite diagnosis of salivary gland carcinosarcoma can only be obtained after complete surgical resection.

Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery.

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules. Using a squamous cell carcinoma model, we demonstrated that a pH-sensitive fusogenic peptide -modification of BMSC-EVs achieved targetability in the microenvironment of a hypoxic tumor to deliver anti-tumor drugs. Using EGFR+HER2- and EGFR-HER2+ breast cancer models, we demonstrated that anti-EGFR and anti-HER2 modifications of BMSC-EVs were able to specifically deliver drugs to EGFR+ and HER2+ tumors, respectively. Using a collagen-induced arthritis model, we confirmed that anti-IL12/IL23-modified BMSC-EVs specifically accumulated in the arthritic joint and alleviated inflammation. Administration of SA-overexpressing BMSC-EVs has limited immunogenicity and high safety in vivo, suggesting that BMSC-derived EVs are ideal drug delivery vehicle. These representative scenarios of targeting modification suggest that, using different biotinylated molecules, the SA-overexpressing BMSC-EVs could be endowed with different targetabilities, which allows BMSC-EVs to serve as a versatile platform for targeted drug delivery under various situations.

HEAP: a task adaptive-based explainable deep learning framework for enhancer activity prediction.

Enhancers are crucial cis-regulatory elements that control gene expression in a cell-type-specific manner. Despite extensive genetic and computational studies, accurately predicting enhancer activity in different cell types remains a challenge, and the grammar of enhancers is still poorly understood. Here, we present HEAP (high-resolution enhancer activity prediction), an explainable deep learning framework for predicting enhancers and exploring enhancer grammar. The framework includes three modules that use grammar-based reasoning for enhancer prediction. The algorithm can incorporate DNA sequences and epigenetic modifications to obtain better accuracy. We use a novel two-step multi-task learning method, task adaptive parameter sharing (TAPS), to efficiently predict enhancers in different cell types. We first train a shared model with all cell-type datasets. Then we adapt to specific tasks by adding several task-specific subset layers. Experiments demonstrate that HEAP outperforms published methods and showcases the effectiveness of the TAPS, especially for those with limited training samples. Notably, the explainable framework HEAP utilizes post-hoc interpretation to provide insights into the prediction mechanisms from three perspectives: data, model architecture and algorithm, leading to a better understanding of model decisions and enhancer grammar. To the best of our knowledge, HEAP will be a valuable tool for insight into the complex mechanisms of enhancer activity.

Developments and trends of endoscopic salivary gland resection: from endoscope-assisted to full endoscopic.

More than 30 years of rapid development of endoscopic surgery has led to the mainstreaming of this procedure in many surgical departments in China. Since the first report on endoscopy, it has been used in salivary gland resection for more than 20 years. The overall development of endoscopic surgery indicates that its use in oral and maxillofacial surgery is still in the early exploration stage; it has not yet been maturely developed or applied. Owing to the advancement of other disciplines and corresponding widening experiences in those fields, the development of endoscopic technology in oral and maxillofacial surgery will likely achieve a leapfrogging. Learning from the general development pattern of endoscopy, this research explores the application history, current situation, and future direction of the application of endoscopy in salivary gland surgery.

Reconstruction of Buccal-penetrating Defects Using the Double-folded Lateral Arm Free Flap.

The reconstruction of buccal-penetrating defects remains challenging. The present study aims to explore the application value of the lateral arm free flap (LAFF) on the reconstruction of buccal-penetrating defects with the hope of providing a better option for clinical practice. Nineteen patients with this kind of issue posed by either tumor resections or deformities in the craniofacial regions were recruited in this study, and LAFF was employed to reconstruct these defects by double folding and individually designing the flap. All the flaps prepared for these subjects in our study survived, and the postoperative assessment of these subjects receiving LAFF revealed that this approach to managing buccal-penetrating defects is able to achieve satisfactory results in terms of appearance and functional recovery. Therefore, our study suggests that LAFF is 1 of the promising flaps to reconstruct the buccal-penetrating defects.

CCL2 promotes lymphatic metastasis via activating RhoA and Rac1 pathway and predict prognosis to some extent in tongue cancer.

BACKGROUND: Oral tongue cancer is an extremely malignant tumor with high rate of lymphatic metastasis. Little is known about its invasion and metastasis mechanisms so far. METHODS: To clarify the main role of CCL2 in tongue cancer progression, we performed Transwell migration assay to confirm the effects of different concentrations of CCL2 on the migration and invasion of tongue cancer cells. Next, by siRNA interference of RhoA and Rac1 in LNMTca8113 cells, we are able to observe that these two molecules block the effect of CCL2 on cell migration and cytoskeleton reorganization by laser confocal microscopy. Moreover, the AKT phosphorylation level of PI3K downstream molecule under the action of CCL2 also be detected by qRT-PCR and western blot, so as to determine whether CCL2 affects the proliferation of LNMTca8113 cells through PI3K/AKT pathway. Finally, we analyzed the relationship between plasma CCL2 level and various clinicopathological parameters in patients with tongue cancer. Results: We found that tongue cancer cells treated with CCL2 migrate faster at first. CCL2 may enhance the invasion and migration of LNMTca8113 cells by activating RhoA and Rac1 to promote cytoskeleton reorganization. Promotion of LNMTca8113 migration induced by CCL2 was inhibited by silence of RhoA and Rac1. CCL2 could increase the phosphorylation of downstream Akt/PI3K signal and promoted the proliferation. Plasma concentration confirmed that the CCL2 level was closely related to the clinical stage of tongue cancer. Patients with lower CCL2 levels had a relatively longer progression-free survival and total survival time. RESULTS: After adding CCL2, the number of proliferation and migration of tongue cancer cells increased and the expression of RhoA and Rac1 rose up in LNMTca8113 cell line. The cytoskeleton reorganization was notable. Patients with higher serum levels of CCL2 had shorter progression-free survival than those with lower levels of CCL2 (P < 0.0001). CONCLUSIONS: CCL2 promotes the invasion and metastasis of tongue cancer by PI3K/Akt pathway. The plasma level of CCL2 may predict prognosis of tongue cancer patients. CCL2 can serve as a potential therapeutic target for tongue cancer treatment.

Increased CCL2 concentration is associated with short- term progress-free survival.CCL2 levels predict patient prognosis are similar to TNM staging.CCL2 levels may be a preferable biomarker for predicting the prognosis of patients with tongue cancer.

Gasless Endoscopic Submandibular Gland Excision Through Hairline Approach.

BACKGROUND: The aim of this study was to evaluate the therapeutic effect of gasless endoscopic submandibular gland excision through hairline approach and the safety, feasibility and practicability of this technique. METHODS: Twenty-five patients with submandibular gland lesions who underwent gasless endoscopic submandibular gland excision through hairline approach at the Department of Head and Neck Oncology of the West China Hospital of Stomatology from May 1 st 2021 to May 31 st 2022 were included in this prospective study. The variables were analyzed statistically with SPSS software version 23.0 (IBM Corp, Armonk, New York, USA). RESULTS: There was a female predominance (72%), female to male ratio was 2.6. The mean age was 30.6±10.2 years (range: 11 to 52 year). All 25 cases of endoscopic submandibular gland excision through hairline approach were done without conversion to conventional approach. This approach was indicated in 14 cases (56%) for pleomorphic adenoma, 8 cases (32%) for chronic sialadenitis, 2 cases (8%) for adenoid cystic carcinoma, and 1 case (4%) for lymphadenitis. The incision length mean was 4.8±0.4 mm (range: 4 to 5 mm); the operation duration mean was 100.6±39.7 min (range: 51 to 197 min); the intraoperative bleeding mean was 13.2±5.7 ml (range: 5 to 20 ml); the hospital length of stay mean was 4.5±0.8 days (range: 3 to 6 days). The follow-up mean was 10±3.4 months (range: 5 to 16 months). The patients were very satisfied with postoperative cosmetic result (score mean: 9.2±1). No recurrence of disease and complications such as postoperative bleeding, hematoma, nerve damage, skin necrosis, infection, and hair loss occurred. CONCLUSIONS: Gasless endoscopic submandibular gland excision through hairline approach is safe, feasible and practicable, resulting in a very satisfied cosmetic result without significant complications; the intraoperative bleeding is less, the operative field is clear, the operation duration decreases with accumulation of experience.

CXCL1 promoted the migration and invasion abilities of oral cancer cells and might serve as a promising marker of prognosis in tongue cancer.

BACKGROUND: Oral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma. METHODS: Cell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull-down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed. RESULTS: CXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression-free survival and overall survival. CONCLUSIONS: CXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.

90 K increased delivery efficiency of extracellular vesicles through mediating internalization.

Using mass spectrometry-based high-throughput proteomics, we identified a membrane protein on extracellular vesicles (EVs), 90 K, which predicts poor overall survival of patients with head and neck cancer. 90 K levels in serum EVs could serve as an independent factor for poor prognosis of patients with head and neck cancer. Pre-treatment of immune competent mice with tumor-derived EVs (TDEs) elicited an immune-suppressive microenvironment for tumor cells, which was regulated by 90 K. The immunosuppressive function of TDE-90 K depends on the presence of myeloid derived suppressor cells (MDSCs) rather than regulatory T cells. The immune regulatory role of TDEs on MDSCs depends on miR-21 which is encapsulated in TDEs. Moreover, 90 K is required for the internalization of TDE cargo though interacting with integrin-ß1 and anti-siglec-9 rather than directly affecting the immune function of MDSCs. 90 K modification of γδT cell-derived EVs (γδTEVs) could increase the delivery efficiency and therapeutic effect of PD-L1 siRNA by γδTEVs. We concluded that as a secreted protein modulating cell-cell and cell-matrix interactions, 90 K can be carried by TDEs to mediate the internalization and delivery of TDEs cargo by recipient cells. This function of 90 K could be utilized to improve the efficiency of EV-based drug delivery.