A new and widely distributed species of Ichthyurus Westwood, 1848 (Cantharidae, Chauliognathinae, Ichthyurini) from China.

Background: The genus Ichthyurus Westwood, 1848 is a large cantharid group consisting of approximately 200 species worldwide, with only 10 species hitherto found in China. Despite its expansive area, the Chinese fauna has historically received little attention from specialists, leading to a lack of knowledge even about some common Ichthyurus species in this region. New information: A new species of Ichthyurus Westwood, 1848 is described under the name of I.longulus sp. nov., which is widely distributed in mainland China, including Shannxi, Gansu, Hubei, Chongqing, Guizhou and Guangxi. Although there are some variations in the pronotum colouration within the species, this new species could be easily distinguished from all others of Ichthyurus by the large-sized body, uniformly black elytra, mesotibiae each with an apical spur in male, terminal abdominal tergite of male with long and cylindrical lateral projections that are about 3/5 the length of the tergite, terminal abdominal ventrite of male saddle-shaped and deeply cleft in middle of apical 2/3 part and aedeagus with a long setifore extension that is as long as the parameres. The habitus, terminal abdominal ventrite and tergites and genitalia of both sexes are illustrated. In addition, a distribution map of this species and a list of the Ichthyurus species from mainland China are provided.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

OBJECTIVE: Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). METHODS: Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. RESULTS: Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. CONCLUSIONS: Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

Increased tumor-infiltrating plasmacytoid dendritic cells express high levels of PD-L2 and affect CD8+ T lymphocyte infiltration in human laryngeal squamous cell carcinoma.

The infiltration and prognostic significance of tumor-infiltrating plasmacytoid dendritic cells (TI-pDC) have been elucidated in various human solid cancers. However, the infiltrating patterns and functional importance of TI-pDC in laryngeal squamous cell carcinoma (LSCC) remain unknown. In this study, flow cytometric analyses were conducted to characterize the infiltration of dendritic cells and T lymphocytes, along with their respective subgroups in tumor tissues (TT), para-carcinoma tissues (PT), and peripheral blood (PB) from LSCC patients. Immunohistochemical staining for CD4 and CD8, as well as immunofluorescence staining for CD123, were performed on serial tissue sections to investigate the co-localization of TI-pDC and tumor-infiltrating T lymphocytes (TIL) within the tumor microenvironment (TME). Our results demonstrated significantly lower percentages of all three DC subsets in PB compared to TT and PT. Notably, the pDC percentage was markedly higher in TT than in PT. Moreover, TI-pDC percentage was significantly elevated in N+ stage patients compared to those with N0 stage. The results of survival analysis consistently demonstrated that high levels of TI-pDC infiltration were indicative of a poor prognosis. Further investigation revealed a significant negative correlation between TI-pDC and CD8+ TILs; notably, pDCs expressed an inhibitory surface molecule PD-L2 rather than PD-L1 within PT. Collectively, our findings suggest that increased TI-pDC is associated with adverse outcomes in LSCC patients while exhibiting an inhibitory phenotype that may play a crucial role in suppressing CD8+ TILs within LSCC tumors. These results highlight the potential therapeutic strategy targeting PD-L2+ pDCs for immunotherapies against LSCC.

Peripheral lymphocyte count as an indicator of radiotherapy effectiveness in hypopharyngeal squamous cell carcinoma.

OBJECTIVES: To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of pathologically confirmed HPSCC patients who had definitive radiation between January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO-based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). MAIN OUTCOME MEASURES AND RESULTS: RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. CONCLUSION: In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT.

The value of multimodal treatment in anaplastic thyroid cancer patients with distant metastasis.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with a poor prognosis, particularly in patients presenting with distant metastasis (DM). This study aimed to assess the effect of combination treatment strategies on survival in ATC patients with DM. METHODS: A retrospective analysis was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) database to identify primary ATC cases with DM at diagnosis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent risk factors for survival. RESULTS: Of the 315 ATC patients with DM included in the study, surgery to the primary tumor, radiotherapy, chemotherapy, and lung metastasis were identified as independent risk factors for survival. Patients who received primary tumor surgery plus chemotherapy or surgery plus chemoradiation exhibited a superior outcome compared to those who received only one treatment modality. CONCLUSION: Our findings suggest that a combination treatment approach, particularly surgery combined with radiotherapy or surgery combined with chemoradiotherapy, may provide the most optimal treatment option for ATC patients with DM. These results may provide some evidence for clinical decision making, but larger sample cohorts are still needed for validation.

Prognostic significance and immune escape implication of tumor-infiltrating neutrophil plasticity in human head and neck squamous cell carcinoma.

Tumor-infiltrating neutrophils play a crucial role in the progression of head and neck squamous cell carcinoma (HNSCC). Here, we aimed to statistically quantify the plasticity of HNSCC-infiltrating N2/N1 neutrophils and examine its impacts on survival and immune infiltration landscape. A retrospective study of 80 patients who underwent curative surgical resection for HNSCC between 2014 and 2017 was conducted in this study. HNSCC-infiltrating neutrophil phenotypes were classified using immunofluorescence staining, and the N2/N1 neutrophil plasticity was evaluated via the ratio of N2/N1 neutrophils. We then assessed the correlations between N2/N1 neutrophil plasticity, clinicopathological characteristics, and immune infiltration landscape using rigorous statistical methods. Infiltration variations of N1 and N2 neutrophils were observed between the tumor nest (TN) and tumor stroma (TS), with TN exhibiting higher N2 neutrophil infiltration and lower N1 neutrophil infiltration. High ratios of N2/N1 neutrophils were correlated with advanced TNM stage, large tumor size and invasion of adjacent tissue. High infiltration of N2 neutrophils was associated with decreased overall and relapse-free survival, which were opposite for N1 neutrophils. The independent prognostic role of N2/N1 neutrophil plasticity, particularly within the TN region, was confirmed by multivariate analyses. Moreover, the ratio of N2/N1 neutrophils within the TN region showed correlations with high CD8+ T cells infiltration and low FOXP3+ Tregs infiltration. We identify HNSCC-infiltrating N2/N1 neutrophil plasticity as a crucial prognostic indictor which potentially reflects the tumor microenvironment (TME) and immune escape landscape within HNSCC tissues. Further investigations and validations may provide novel therapeutic strategies for personalized immunomodulation in HNSCC patients.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.

Standard: Human intestinal organoids.

Organoids have attracted great interest for disease modelling, drug discovery and development, and tissue growth and homeostasis investigations. However, lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications. "Human intestinal organoids" is the first guideline on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods, inspection rules for human intestinal organoids, which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids. It was originally released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.

Standard: Human intestinal cancer organoids.

Intestinal cancer is one of the most frequent and lethal types of cancer. Modeling intestinal cancer using organoids has emerged in the last decade. Human intestinal cancer organoids are physiologically relevant in vitro models, which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer. "Human intestinal cancer organoids" is the first set of guidelines on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods for human intestinal cancer organoids, which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids. It was released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practocal protocols, and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.

High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma.

BACKGROUND: HLA-DR is expressed in epithelial and several types of tumor cells. However, the correlation between tumor-expressed HLA-DR (teHLA-DR) and patient outcome as well as its regulation on the tumor microenvironment (TME) of laryngeal squamous cell carcinoma (LSCC) are yet to be elucidated. METHODS: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. teHLA-DR tumor cell, CD4+ and CD8+ tumor-infiltrating T lymphocytes (TITLs) were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method and tested by the log-rank test method. Expression of teHLA-DR+ tumor cells and infiltration of T lymphocytes and their corresponding subgroups were analyzed by flow cytometry using fresh LSCC tissue samples. RESULTS: Our research discovered elevated expressions of multiple MHC-II-related genes in tumor compared to the adjacent normal tissue samples of LSCC patients. We also found that patients in the teHLA-DR high-expression group (teHLA-DRhigh) tend to have less tumor recurrence and better survival outcomes compared to those in the teHLA-DRlow group. Intriguingly, teHLA-DR+ tumor cells had significantly higher PD-L1 and PD-L2 expression and their TME showed increased infiltrated T lymphocytes (TITLs). Flow cytometry analysis and IHC staining indicated that CD4+ TITLs but not CD3+ total TITLs or CD8+ TITLs were significantly enriched in teHLA-DR+ tumors. CONCLUSIONS: teHLA-DR may be a predictive marker for favorable prognosis and response to anti-PD-1/PD-L1 therapy of LSCC, possibly due to the increased CD4+ TITLs in the TME.

miR-34a/DRP-1-mediated mitophagy participated in cisplatin-induced ototoxicity via increasing oxidative stress.

PURPOSE: Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. METHODS: In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. RESULTS: MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. CONCLUSION: MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

CD206+ tumor-associated macrophages interact with CD4+ tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma.

BACKGROUND: Tumor-associated macrophages (TAMs) are major component in the tumor microenvironment (TME) and play regulatory role in tumor progression. We aimed to investigate the infiltration and prognostic value of TAMs in laryngeal squamous cell carcinoma (LSCC) and to reveal the underlying mechanism of TAM subgroups in tumorigenesis. METHODS: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. CD206 + /CD163 + and iNOS + TAM infiltrating profiles were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves based on the infiltration of TAMs were plotted using the Kaplan-Meier method. Infiltration of macrophages, T lymphocytes and their corresponding subgroups were analyzed in fresh LSCC tissue samples by flow cytometry. RESULTS: We found that CD206+ rather than CD163+ M2-like TAMs were the most enriched population in the TME of human LSCC. CD206+ macrophages localized mostly in the tumor stroma (TS) rather than the tumor nest (TN) region. In contrast, relatively low infiltration of iNOS+ M1-like TAMs were found in the TS and almost none in the TN region. High level of TS CD206+ TAM infiltration correlated with poor prognosis. Interestingly, we identified a HLA-DRhigh CD206+ macrophage subgroup that was significantly associated with the tumor-infiltrating CD4+ T lymphocytes and showed different surface costimulatory molecule expression than that of the HLA-DRlow/-CD206+ subgroup. Taken together, our results indicate that HLA-DRhigh-CD206+ is a highly activated subgroup of CD206 + TAMs that may interact with CD4 + T cells through MHC-II axis and promote tumorigenesis.

Time-varying association of second primary malignancy and long-term survival outcomes in patients with head and neck cancer.

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP-HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time-varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP-HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow-up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20-3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP-HNSCC vs regional IP-HNSCC (HROS , 3.41; 95% CI: 3.24-3.6 vs HROS , 3.18; 95% CI: 3.05-3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.

Heterogeneity and subtypes of CD4+ regulatory T cells: implications for tumor therapy.

In the conventional view, CD4+ regulatory T cell (Treg) represents a subset of lymphocytes that involve the perception and negative regulation of the immune response. CD4+Treg plays an important role in the maintenance of immune homeostasis and immune tolerance. However, recent studies have revealed that CD4+Treg do not suppress the immune response in some diseases, but promote inflammatory injury or inhibit tissue remodeling, suggesting the functional heterogeneity of CD4+Treg. Their involvement in tumor pathogenesis is more complex than previously understood. This article reviews the relevant research on the heterogeneity of CD4+Treg, subtype classification, and their relationship with tumor therapy.

Recurrence risk stratification and treatment strategies of patients with stage IVa-b hypopharyngeal squamous cell carcinoma.

BACKGROUND: Optimal treatment strategies for patients with stage IVa-b hypopharyngeal squamous cell carcinoma (HSCC) remain controversial. This study aimed to examine the high-risk factors of postoperative tumor recurrence after surgical resection of HSCC and devise individualized postoperative adjuvant treatment (POAT). METHODS: Overall, 218 patients with stage IVa-b HSCC who received surgery as initial treatment and with negative surgical margins were evaluated. Independent risk factors of recurrence were identified, and survival outcomes were compared according to recurrence risk and POAT use. RESULTS: POAT significantly improved recurrence-free survival (RFS) and overall survival (OS) only in the high-risk patients (p = 0.003 and 0.018, respectively). Compared with postoperative radiotherapy alone, postoperative chemoradiotherapy (pCRT) achieved significantly better RFS (p = 0.035) and OS (p = 0.048). CONCLUSIONS: POATs are recommended for high-risk patients with stage Iva-b HSCC, with pCRT achieving superior outcomes. Regular re-examination after tumor resection is sufficient for low-risk patients.

Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer.

To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis coli (APC) gene mutations in CRC patients. A total of 238 Chinese CRC patients was retrospectively identified and analyzed for clinical features and gene alternations in APC-mutant type (MT) and APC-wild-type (WT) groups. Clinical responses were then evaluated from the public TCGA database and MSKCC immunotherapy database. Although programmed cell death ligand 1 (PD-L1) level, MSI status, loss of heterogeneity at the human leukocyte antigen (HLA LOH), and tumor neoantigen burden (TNB) level were not statistically different between the APC-MT group and APC-WT group, tumor mutation burden (TMB) level was significantly higher in APC-MT patients (P < 0.05). Furthermore, comutation analysis for APC mutations revealed co-occurring genomic alterations of PCDHB7 and exclusive mutations of CTNNB1, BRAF, AFF3, and SNX25 (P < 0.05). Besides, overall survival from MSKCC-CRC cohort was longer in the APC-WT group than in the APC-MT group (HR 2.26 (95% CI 1.05-4.88), P < 0.05). Furthermore, most of patients in the APC-WT group were detected as high-grade immune subtypes (C2-C4) comparing with those in the APC-MT group. In addition, the percentages of NK T cells, Treg cells, and fibroblasts cells were higher in APC-WT patients than in APC-MT patients (P < 0.05). In summary, APC mutations might be associated with poor outcomes for immunotherapy in CRC patients regardless of MSI status. This study suggested APC gene mutations might be a potential predictor for immunotherapy in CRC.

Management of clinically node-negative glottic squamous cell carcinoma patients according to risk-scoring model for occult lymph node metastases.

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.

The Prognostic Capacity of Systemic Inflammation Response Index, Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in Patients with Hypopharyngeal Squamous Cell Carcinoma.

INTRODUCTION: Systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been proposed as peripheral blood biomarkers. We compared these blood biomarkers to identify the best predictor in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: We conducted a retrospective study on 304 patients with HPSCC. SIRI was divided into three groups using X-tile version 3.6.1. The optimal cut-off points for NLR, LMR, and PLR were selected through RStudio. We compared the prognostic capacity of SIRI with that of NLR, LMR, and PLR using receiver operating characteristic curves. RESULTS: Smoking, cancer in the postcricoid region, lymph node metastasis (N+), extracapsular invasion, SIRI in the highest tertile (>2.80), and LMR in the lowest tertile (<5.0) may cause poor 5-year overall survival (OS) in patients with HPSCC. Local and distant recurrences may occur earlier in those with lymph node metastasis and a tumor invading beyond the mucosa layer. CONCLUSIONS: SIRI was a better predictor of OS than LMR, PLR, and NLR in HPSCC patients. SIRI in the highest tertile (>2.80) and LMR in the lowest tertile (<5.0) may cause poor 5-year OS.

Tumor-Infiltrating PD-L1+ Neutrophils Induced by GM-CSF Suppress T Cell Function in Laryngeal Squamous Cell Carcinoma and Predict Unfavorable Prognosis.

PURPOSE: Chronic inflammation contributes to tumor initiation, progression, and immune escape. Neutrophils are the major component of inflammatory response and participate in the tumorigenesis process. However, compared to other immune cells in the tumor microenvironment of laryngeal squamous cell carcinoma (LSCC), neutrophils, especially the tumor-associated neutrophils (TANs), have not yet been comprehensively explored. The mechanism for regulating the crosstalk between TANs and tumor cells still remains unclear. MATERIALS AND METHODS: The distribution profiles and phenotypic features of neutrophils and other inflammatory immune cell populations from a large LSCC patient cohort were systemically analyzed. Co-culturing of peripheral blood associated neutrophils (PANs) and TANs with PBMCs was performed, and the immunosuppression effect on T-cells was examined. RESULTS: LSCC microenvironment is highly inflammatory with remarkable TANs infiltration, which is often associated with unfavorable prognosis and advanced clinical stage. We find that TANs in LSCC display morphologically immature and lower apoptosis, exhibit distinctively immunosuppressive phenotype of high PD-L1, and suppress CD8+ T lymphocytes proliferation and activation. We subsequently discover that PD-L1+TANs induced by LSCC-derived GM-CSF potently impair CD8+ T-cells proliferation and cytokines production function, which are partially blocked by a PD-L1-neutralizing antibody. Clinical data further support GM-CSF as an unfavorable prognostic biomarker and reveal a potential association with inflammatory immune cell infiltration, in particular neutrophils. CONCLUSION: Tumor-infiltrating PD-L1+ neutrophils induced by LSCC-derived GM-CSF suppress T cell proliferation and activation in the inflammatory microenvironment of LSCC and predict unfavorable prognosis. These TANs cripple antitumor T cell immunity and promote tumor progression. Our findings provide a basis for targeting PD-L1+TANs or GM-CSF as a new immunotherapeutic strategy for LSCC.

[Postoperative prognostic risk factors and treatment strategies for patients with T3-T4 hypopharyngeal squamous cell carcinoma].

Objective:To investigate the independent prognostic risk factors and the application of different postoperative adjuvant treatment strategies on patients with T3-T4 hypopharyngeal carcinoma. Methods:Based on the inclusion criteria, we conducted a retrospective study that analyzed the clinical data of 229 cases who underwent surgery at the Eye, Ear, Nose and Throat Hospital of Fudan University from 2003 to 2015. Risk factors for postoperative survival were analyzed by univariate and multivariate analysis and patients were stratified according to the independent risk factors. The efficacy of various postoperative adjuvant therapystrategies were compared in different risk groups. Results:Two hundred and twenty-nine patients with T3-T4 primary tumor had 3-year and 5-year overall survival rates of 39.07% and 29.03%, respectively; 3-year and 5-year recurrence-free survival rates were 40.22% and 30.29%, respectively. The results of multivariate analysis demonstrated that tumors in the posterior pharyngeal wall and posterior cricoid region, N2c-N3, lymphovascular invasion, and extranodal extension were independent risk factors. The utility of postoperative adjuvant therapy significantly improved postoperative survival in the high-risk group （P<0.05） and reduced postoperative recurrence significantly （P<0.01）. Patients received adjuvant chemoradiation had better survival than those received adjuvant radiation alone （P<0.05）. Postoperative adjuvant therapy had no significant effect on postoperative survival of patients in the low-risk group. Conclusion:Independent risk factors for patients with T3-T4 hypopharyngeal carcinoma include tumors in the posterior pharyngeal wall and posterior cricoid region, N2c-N3, lymphovascular invasion, as well as extranodal extension. Postoperative adjuvant therapy, especially adjuvant chemoradiation,is recommended for patient with risk factors mentioned above. For patients without those risk factors, postoperative follow-up and re-examination are recommended.