Radiation-induced fibrosis: Mechanisms and therapeutic strategies from an immune microenvironment perspective.

Radiation-induced fibrosis (RIF) is a severe chronic complication of radiotherapy (RT) manifested by excessive extracellular matrix (ECM) components deposition within the irradiated area. The lung, heart, skin, jaw, pelvic organs and so on may be affected by RIF, which hampers body functions and quality of life. There is accumulating evidence suggesting that the immune microenvironment may play a key regulatory role in RIF. This article discussed the synergetic or antagonistic effects of immune cells and mediators in regulating RIF's development. Several potential preventative and therapeutic strategies for RIF were proposed based on the immunological mechanisms to provide clinicians with improved cognition and clinical treatment guidance.

FADD amplification is associated with CD8+ T-cell exclusion and malignant progression in HNSCC.

OBJECTIVE: This study aimed to clarify the relationship between FADD amplification and overexpression and the tumor immune microenvironment. METHODS: Immunohistochemical staining and bioanalysis were used to analyze the association between FADD expression in tumor cells and cells in tumor microenvironment. RNA-seq analysis was used to detect the differences in gene expression upon FADD overexpression. Flow cytometry and multicolor immunofluorescence staining (mIHC) were used to detect the differences in CD8+ T-cell infiltration in FADD-overexpressed cells or tumor tissues. RESULTS: Overexpression of FADD significantly promoted tumor growth. Cells with high FADD expression presented high expression of CD276 and FGFBP1 and low expression of proinflammatory factors (such as IFIT1-3 and CXCL8), which reduced the percentage of CD8+ T cells and created a "cold tumor" immune microenvironment, thus promoting tumor progression. In vivo and in vitro experiment confirmed that tumor tissues with excessive FADD expression exhibited CD8+ T-cell exclusion in the microenvironment. CONCLUSION: Our preliminary investigation has discovered the association between FADD expression and the immunosuppressive microenvironment in HNSCC. Due to the high frequent amplification of the chromosomal region 11q13.3, where FADD is located, targeting FADD holds promise for improving the immune-inactive state of tumors, subsequently inhibiting HNSCC tumor progression.

Intratumoral tertiary lymphoid structures promote patient survival and immunotherapy response in head neck squamous cell carcinoma.

Tertiary lymphoid structures (TLSs) hold the potential role in the prediction of immunotherapy response in several clinical trials. TLSs in head neck squamous cell carcinoma (HNSCC) have been investigated through IHC analysis, whereas there is no TLS gene signature to evaluate the level of TLS neogenesis. We here proposed a TLS signature containing 13 chemokines and determined TLS-hi and TLS-low groups in HNSCC samples from The Cancer Genome Atlas. TLS-hi condition signified a better overall survival. A more inflamed immune infiltrative landscape was identified in the TLS-hi tumors characterized by higher proportion of T cells, TCR/BCR activation and antigen processing. High level of TLSs has a determined role in the clinical significance of T cells. Interesting discovery was that innate lymphoid cells and cancer-associated fibroblasts were positively associated with TLS neogenesis in TME of HNSCC. Furthermore, by integrated TLSs with stromal cells and score, immune cells and score, TMB and malignant cells, we proposed a novel HNSCC TME classifications (HNSCC-TCs 1-5), unravelling the counteracted role of stromal cells and score in inflamed immune landscape, which may provide a novel stromal targeted modality in HNSCC therapy. Finally, we verified that TLS statue is an ideal predictor for immune checkpoint blockade immunotherapy. Current study indicated that the TLSs serve as a novel prognostic biomarker and predictor for immunotherapy, which may provide directions to the current investigations on immunotherapeutic strategies for HNSCC.

Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws.

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.

A Sonication-Activated Valence-Variable Sono-Sensitizer/Catalyst for Autography Inhibition/Ferroptosis-Induced Tumor Nanotherapy.

The effective deployment of reactive oxygen species (ROS)-mediated oncotherapy in practice remains challenging, mired by uncontrollable catalytic processes, stern reaction conditions and safety concerns. Herein, we develop a copper nanodot integrating sonodynamic and catalytic effects within one active center, which responds to exogenous ultrasound (US) and endogenous H2 O2 stimuli. US irradiation induces the valence conversion from CuII to CuI catalyzing H2 O2 into ⋅OH for chemodynamic therapy. Meanwhile, valence transformation results in electron-hole pairs separation, promoting ROS generation for sonodynamic therapy. Notably, copper nanodots not only block lysosome fusion and degradation leading to autophagy flux blockage, but also interfere with the glutathione peroxidase 4 and cystine-glutamate antiporter SLC7A11 function achieving ferroptosis. Furthermore, reversible valence changes, inherent hydrophilicity and renal clearance ultrasmall size guarantee biosafety.

Salvage surgery for patients with residual/persistent diseases after improper or insufficient treatment of oral squamous cell carcinoma: can we rectify these mistakes?

BACKGROUND: Patterns of failure after treatment of oral and squamous cell carcinomas (OSCC) are diversified, with recurrences being one of the common causes. A special group of patients are sometimes encountered in the outpatient clinic for improper or insufficient initial treatment with reports of positive margins, implying residual/persistent diseases. The question of whether these patients can be surgically salvaged remain unanswered. METHODS: A retrospective study was performed between January 2013 and December 2017 for patients with residual or rapid recurrent (within 3 months) OSCCs, who received salvage surgeries in our institution. The patients with residual/persistent OSCCs were those with microscopic or macroscopic positive surgical margins, while those with rapid recurrent OSCCs were those with close or negative margins, but unabated painful symptoms right after treatment. Both clinicopathological and prognostic variables were analyzed. The focus was also directed towards lessons for possible initial mistakes, resulting in these residual/persistent diseases. RESULTS: Of 103 patients, 68 (66%) were men, with mean age of 56.3 years. The overall survival reached 60.2%. Regarding the primary OSCC status, most of our patients (n = 75, 72.8%) were diagnosed with ycT2-3 stages. Besides, most patients were found with macroscopic residual diseases (52.4%) before our salvage surgery. The sizes of the residual/persistent OSCCs were generally under 4 cm (87.3%) with minimally residual in 21 (20.4%). Among all the variables, primary T stage (p = 0.003), and residual lesion size (p < 0.001) were significantly associated with the prognosis in multivariate analysis. Though the causes for the initial surgical failure were multifactorial, most were stemmed from poor planning and unstandardized execution. CONCLUSIONS: Cases with residual/persistent OSCCs were mostly due to mistakes which could have been avoided under well-round treatment plans and careful surgical practice. Salvage surgery for cases with smaller residual/persistent OSCCs is still feasible with acceptable outcomes.

The opposite functions of miR-24 in the osteogenesis and adipogenesis of adipose-derived mesenchymal stem cells are mediated by the HOXB7/ß-catenin complex.

Adipose-derived mesenchymal stem cells (ADMSCs) used in combination with nanoparticles or scaffolds represent promising candidates for bone engineering. Compared to bone marrow-derived MSCs (BMMSCs), ADMSCs show a relatively low capacity for osteogenesis. In the current study, miR-24 was identified as an osteogenesis- and adipogenesis-related miRNA that performs opposing roles (inhibition in osteogenesis and promotion in adipogenesis) during these two differentiation processes. Through bioinformatics analysis and luciferase reporter assays, homeobox protein Hox-B7 (HOXB7) was identified as a potential novel downstream target of miR-24 that contains a miR-24 binding site in the 3'-UTR of its mRNA. Overexpression of HOXB7 could partly halt the inhibitory effect of miR-24 on osteogenesis, and downregulation of HOXB7 could also partly suppress the positive effect of miR-24 on adipogenesis. Furthermore, immunoprecipitation experiments found that HOXB7 and ß-catenin formed a functional complex that acted as an essential modulator during osteogenesis and adipogenesis of ADMSCs. After transfecting ADMSCs with an MSNs-PEI-miR-24 agomir or antagomir and loading the cells onto gelatin-chitosan scaffolds, the compounds were assessed for their abilities to repair the critical-sized calvarial defects in rats. Comprehensive evaluation, including micro-CT, sequential fluorescent labeling, and immunohistochemistry analysis, revealed that silencing miR-24 distinctly promoted in vivo bone remolding, whereas overexpression of miR-24 significantly repressed bone formation. Taken together, our findings demonstrated opposite roles for the miR-24/HOXB7/ß-catenin signaling pathway in the osteogenesis and adipogenesis of ADMSCs, which may provide a novel mechanism for determining the balance between these two biological processes.

Reconstruction With Fibula Musculocutaneous Flap in a Patient With Extensive Maxillary Osteoradionecrosis.

The authors reported a case of extensive maxillary osteoradionecrosis. The maxilla was resected and reconstructed with fibula musculocutaneous flap. It was the first reported that the osteoradionecrotic maxilla was reconstructed with free vascularized bone. The musculocutaneous flap might be a better choice of maxillary osteoradionecrosis reconstruction instead of the simple soft-tissue flap.

An Odontogenic Keratocyst in the Temporal Region.

The authors report a very rare patient with ectopic odontogenic keratocyst (OKC) in the temporal region that is distant form the mandible. Based on the interesting report, they discuss about the possible origin and illustrate the development of the ectopic OKC. It shows that the OKC could distally relapse with the help of temporal muscle. The surgeon should be more proactive to deal with the peripheral muscle of lesion.

XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-ß1-stimulated C3H10T1/2 cells via Smad2/4.

Pirfenidone is an orally bioavailable synthetic compound with therapeutic potential for idiopathic pulmonary fibrosis. It is thought to act through antioxidant and anti-fibrotic pathways. Pirfenidone inhibits proliferation and/or myofibroblast differentiation of a wide range of cell types, however, little studies have analyzed the effect of pirfenidone on the mesenchymal stem cells, which play an important role on the origin of myofibroblasts. We recently found that pirfenidone had anti-proliferative activity via G1 phase arrest and cell division cycle 7 (Cdc7) kinase expression decrease in transforming growth factor-ß1 (TGF-ß1)-stimulated murine mesenchymal stem C3H10T1/2 cells. Pirfenidone also had inhibiting effect on the migration and α-SMA expression. Moreover, in this study we showed for the first time that Cdc7 inhibitor XL413 enhanced the anti-fibrotic activity of pirfenidone via depressed the expression of Smad2/4 proteins, and also prevented the nuclear accumulation and translocation of Smad2 protein. In conclusion, we demonstrated that pirfenidone inhibited proliferation, migration and differentiation of TGF-ß1-stimulated C3H10T1/2 cells, which could be enhanced by Cdc7 inhibitor XL413, via Smad2/4. Combination with pirfenidone and XL413 might provide a potential candidate for the treatment of TGF-ß1 associated fibrosis. It needs in vivo studies to further validate its therapeutic function and safety in the future.

Management of the primary intraosseous synovial sarcoma of the jaws: be careful of the surgical margin.

PURPOSE: Synovial sarcoma (SS) is extremely rare in the jaws, and only 8 cases have been reported worldwide. The specific aims of this study were to report 15 cases of primary intraosseous SS (PISS) and analyze the histologic features and outcome-related prognostic factors. MATERIALS AND METHODS: Data from patients diagnosed with PISS from 2004 to 2013 were collected in this retrospective study. Patient characteristics (primary location, histologic subtype, tumor size, and surgical margin) were defined as predictor variables. Local recurrence and tumor-related death were outcome variables. The association of tumor-related outcomes with patient characteristics was analyzed using Kaplan-Meier and Cox regression statistics. Other clinical and pathologic characteristics were summarized as a third category of variables for further analysis. RESULTS: This study examined 15 cases (women, n = 10; men, n = 5) with a mean age at diagnosis of 35 years. There was no imbalance in the distribution of primary SS locations (maxilla, n = 7; mandible, n = 8). Six patients (40%) developed local recurrence and 4 patients (26.7%) had a tumor-related death. The 5-year local recurrence-free survival (LRFS) and overall survival rates were 57% and 69.1%, respectively. The strong statistical association of surgical margin with 5-year LRFS rate was shown by univariate (P = .01) and multivariate (hazard ratio = 7.598; P = .028) analyses. CONCLUSIONS: PISS is extremely rare in the jaw. Immunohistochemical analysis played an important role in the diagnosis of PISS. The surgical margin showed a strong association with local recurrence. Thus, ideal surgical margins should be achieved during surgery to obtain better local control.

Microvascular reconstruction in elderly oral cancer patients: does diabetes status have a predictive role in free flap complications?

PURPOSE: Flap complications still present challenges in the field of microsurgical reconstruction. The aim of this study was to explore the role of diabetes mellitus in free flap prognosis in elderly patients (≥60 years) after oral tumor resection. PATIENTS AND METHODS: The data of aged oral cancer patients who had undergone reconstructions with free flaps in our institution were gathered in this retrospective cohort study. The samples were classified into diabetic and nondiabetic groups. The predictive roles of diabetes status and other factors in free flap prognosis were analyzed. The primary outcome variable was the presence of flap complications, which was subdivided into major (requiring re-exploration or local surgery) and minor (dressing or drug treatment) groups. Major complications were defined as the second outcome variable. Univariate and multivariable analyses were used for data statistics. RESULTS: A total of 309 patients (176 men [57%] and 133 women [43%]) aged 60 years or older were included in this study. There were 105 diabetic patients (34%) and 204 nondiabetic patients (66%). A total of 75 flap complications occurred during the perioperative period, with an overall incidence of 24.3% (44 diabetic patients [41.9%] and 31 nondiabetic patients [15.2%], P ≤ .001). The odds of susceptibility for flap complication development in elderly diabetic patients was 3.413 times that of nondiabetic patients (odds ratio, 3.413; P ≤ .001). Of 75 flap complications, 43 (13.9%) were deemed major complications (24 diabetic patients [22.9%] and 19 nondiabetic patients [9.3%], P ≤ .001). This statistical association was further confirmed by multivariate analysis (odds ratio, 2.885; P = .002). CONCLUSIONS: Diabetes mellitus increases the risk of the development of free flap complications in elderly patients when dealing with oral reconstruction after tumor removal.

Single-Cell Analyses Reveal the Metabolic Heterogeneity and Plasticity of the Tumor Microenvironment during Head and Neck Squamous Cell Carcinoma Progression.

Metabolic reprogramming is a hallmark of cancer. In addition to metabolic alterations in the tumor cells, multiple other metabolically active cell types in the tumor microenvironment (TME) contribute to the emergence of a tumor-specific metabolic milieu. Here, we defined the metabolic landscape of the TME during the progression of head and neck squamous cell carcinoma (HNSCC) by performing single-cell RNA sequencing on 26 human patient specimens, including normal tissue, precancerous lesions, early stage cancer, advanced-stage cancer, lymph node metastases, and recurrent tumors. The analysis revealed substantial heterogeneity at the transcriptional, developmental, metabolic, and functional levels in different cell types. SPP1+ macrophages were identified as a protumor and prometastatic macrophage subtype with high fructose and mannose metabolism, which was further substantiated by integrative analysis and validation experiments. An inhibitor of fructose metabolism reduced the proportion of SPP1+ macrophages, reshaped the immunosuppressive TME, and suppressed tumor growth. In conclusion, this work delineated the metabolic landscape of HNSCC at a single-cell resolution and identified fructose metabolism as a key metabolic feature of a protumor macrophage subpopulation. Significance: Fructose and mannose metabolism is a metabolic feature of a protumor and prometastasis macrophage subtype and can be targeted to reprogram macrophages and the microenvironment of head and neck squamous cell carcinoma.

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.

Macrophages and tumour stroma cells account for the main cellular components in the tumour microenvironment (TME). Current advancements in single-cell analysis have revolutionized our understanding of macrophage diversity and macrophage-stroma interactions. Accordingly, this review describes new insight into tumour-associated macrophage (TAM) heterogeneity in terms of tumour type, phenotype, metabolism, and spatial distribution and presents the association between these factors and TAM functional states. Meanwhile, we focus on the immunomodulatory feature of TAMs and highlight the tumour-promoting effect of macrophage-tumour stroma interactions in the immunosuppressive TME. Finally, we summarize recent studies investigating macrophage-targeted therapy and discuss their therapeutic potential in improving immunotherapy by alleviating immunosuppression.

FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-ß1 promotes abnormal glycosylation of SEMA7A via induction of epithelial-mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.

Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer-associated fibroblasts (CAFs) show multiple tumor-promoting effects and can induce tumor immune evasion and drug-resistance. Regulating CAFs can be a potential strategy to augment systemic anti-tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs' tumor-promoting and immune-suppressive phenotypes. Accordingly, a controllable and TME-responsive hydrogen therapy based on a CaCO3 nanoparticles-coated magnesium system (Mg-CaCO3) is developed. The hydrogen therapy by Mg-CaCO3 can not only directly kill tumor cells, but also inhibit pro-tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg-CaCO3 can significantly suppress tumor growth, turn the "cold" primary tumor into "hot", and stimulate systematic anti-tumor immunity, which is confirmed by the bilateral tumor transplantation models of "cold tumor" (4T1 cells) and "hot tumor" (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti-tumor immune stimulating strategy by remodeling tumor stromal microenvironment.

Lipid metabolism marker CD36 is associated with 18FDG-PET/CT false negative lymph nodes in head and neck squamous cell carcinoma.

Background: Lymph node metastasis frequently occurs in head and neck squamous cell carcinoma (HNSCC) patients, and [18F] fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) examination for lymph node metastasis could result in false negativity and delay following treatment. However, the mechanism and resolution for 18FDG-PET/CT false negatives remain unclear. Our study was aim to found biomarkers for false negativity and true positivity from a metabolic perspective. Methods: Ninety-two patients diagnosed with HNSCC who underwent preoperative 18FDG-PET/CT and subsequent surgery in our institution were reviewed. Immunohistochemistry (IHC) examinations of glucose metabolism (GLUT1 and GLUT5), amino acid metabolism4 (GLS and SLC1A5), and lipid metabolism (CPT1A and CD36) markers were conducted on their primary lesion and lymph node sections. Results: We identified specific metabolic patterns of the false-negative group. Significantly, CD36 IHC score of primary lesions was higher in false-negative group than true-positive group. Moreover, we validated pro-invasive biological effects of CD36 by bioinformatics analysis as well as experiments. Conclusion: IHC examination of CD36 expression, which is a lipid metabolism marker, in primary lesions could distinguish HNSCC patients' lymph nodes false negatives in 18FDG-PET/CT.

Enhanced tissue infiltration and bone regeneration through spatiotemporal delivery of bioactive factors from polyelectrolytes modified biomimetic scaffold.

Efficient healing of bone defect is closely associated with the structured and functional characters of tissue engineered scaffolds. However, the development of bone implants with rapid tissue ingrowth and favorable osteoinductive properties remains a challenge. Herein, we fabricated polyelectrolytes modified-biomimetic scaffold with macroporous and nanofibrous structures as well as simultaneous delivery of BMP-2 protein and trace element strontium. The hierarchically structured scaffold incorporated with strontium-substituted hydroxyapatite (SrHA) was coated with polyelectrolyte multilayers of chitosan/gelatin via layer-by-layer assembly technique for BMP-2 immobilization, which endowed the composite scaffold with sequential release of BMP-2 and Sr ions. The integration of SrHA improved the mechanical property of composite scaffold, while the polyelectrolytes modification strongly increased the hydrophilicity and protein binding efficiency. In addition, polyelectrolytes modified-scaffold significantly facilitated cell proliferation in vitro, as well as enhanced tissue infiltration and new microvascular formation in vivo. Furthermore, the dual-factor loaded scaffold significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells. Moreover, both vascularization and new bone formation were significantly increased by the treatment of dual-factor delivery scaffold in the rat calvarial defects model, suggesting a synergistic effect on bone regeneration through spatiotemporal delivery of BMP-2 and Sr ions. Overall, this study demonstrate that the prepared biomimetic scaffold as dual-factor delivery system has great potential for bone regeneration application.

Plac1 Remodels the Tumor Immune Evasion Microenvironment and Predicts Therapeutic Response in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC or HNSC) is the sixth most common cancer worldwide. Placenta-specific 1 (Plac1) belongs to the cancer testis antigen family and is highly expressed in malignant cells in HNSC. However, the biological function and prognostic value of plac1 in HNSC are still unclear. In the current research, we performed a comprehensive analysis of plac1 using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) bulk RNA sequencing databases as well as a single-cell sequencing dataset. We constructed a 15-gene prognostic signature through screening plac1-related immunomodulators and validated its efficiency and accuracy in immunotherapy cohorts and a pancancer database. We found that plac1 expression level is a prognostic predictor of poor overall survival in patients with HNSC. Plac1 is associated with epithelial-mesenchymal transition and tumor invasion. Plac1 has a "dual immunosuppressive function" on tumor microenvironment. On one hand, plac1-positive cells promote extracellular matrix formation and suppress immune cell infiltration. On the other hand, plac1-positive cells enhance the interaction between dendritic cells and macrophages, which further suppresses antitumor immunity. Finally, we constructed a 15-gene prognostic signature, the efficiency and accuracy of which were validated in immunotherapy cohorts and a pancancer database. In conclusion, plac1 is a promising candidate biomarker for prognosis, a potential target for immunotherapy, and a novel point for studying the immunosuppressive mechanisms of the tumor microenvironment in HNSC.

Constrast-enhanced computed tomography radiomics predicts CD27 expression and clinical prognosis in head and neck squamous cell carcinoma.

Objective: This study aimed to construct a radiomics model that predicts the expression level of CD27 in patients with head and neck squamous cell carcinoma (HNSCC). Materials and methods: Genomic data and contrast-enhanced computed tomography (CT) images of patients with HNSCC were downloaded from the Cancer Genome Atlas and Cancer Imaging Archive for prognosis analysis, image feature extraction, and model construction. We explored the potential molecular mechanisms underlying CD27 expression and its relationship with the immune microenvironment and predicted CD27 mRNA expression in HNSCC tissues. Using non-invasive, CT-based radiomics technology, we generated a radiomics model and evaluated its correlation with the related genes and HNSCC prognosis. Results and conclusion: The expression level of CD27 in HNSCC may significantly influence the prognosis of patients with HNSCC. Radiomics based on contrast-enhanced CT is potentially effective in predicting the expression level of CD27.