scholarly journals TNF Patterns and Tumor Microenvironment Characterization in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Long ◽  
Chunyu Huang ◽  
Qi Meng ◽  
Jin Peng ◽  
Fan Yao ◽  
...  
Keyword(s):  
Risk Score ◽  
Immune Cell ◽  
Expression Patterns ◽  
Clustering Methods ◽  
Profile Data ◽  
Immune Microenvironment ◽  
Effector Functions ◽  
Tumor Immune Microenvironment ◽  
Risk Scoring ◽  
Risk Scoring System

BackgroundHNSCC is a heterogeneous disease, which arises from distinct anatomic subsites, associates with various risk factors and possesses diverse molecular pathological features. Generally, HNSCC is considered as an immunosuppressive disease, characterized by abnormal tumor immune microenvironment. The TNF family plays a crucial role in the survival, proliferation, differentiation, and effector functions in both immune and non-immune cells. However, the expression patterns of TNF in HNSCC remains to be systematically analyzed.MethodsWe downloaded transcriptional profile data of HNSCC from TCGA and GEO datasets. Unsupervised clustering methods were used to identify different TNF patterns and classify patients for further analysis. PCA was conducted to construct a TNF relevant score, which we called risk score.ResultsIn this study, we systematically evaluated the patterns of TNF family and tumor immune microenvironment characteristics of HNSCC patients by clustering the expression of 46 members of TNF family. We identified two subtypes with distinct clinical and immune characteristics in HNSCC and constructed a risk scoring system based on the expression profile of TNF family genes.ConclusionRisk score serves as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, which has the potential to be applied as a valuable biomarker for HNSCC immunotherapy.

scholarly journals Tumor Immune Microenvironment Related Gene-Based Model to Predict Prognosis and Response to Compounds in Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiang Yang ◽  
Shasha Hong ◽  
Xiaoyi Zhang ◽  
Jingchun Liu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Killer Cell ◽  
Figo Stage ◽  
The Cancer Genome Atlas ◽  
Immune Microenvironment ◽  
Natural Killer Cell Cytotoxicity ◽  
Tumor Immune Microenvironment

BackgroundThe tumor immune microenvironment (TIME) has been recognized to be an imperative factor facilitating the acquisition of many cancer-related hallmarks and is a critical target for targeted biological therapy. This research intended to construct a risk score model premised on TIME-associated genes for prediction of survival and identification of potential drugs for ovarian cancer (OC) patients.Methods and ResultsThe stromal and immune scores were computed utilizing the ESTIMATE algorithm in OC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network and differentially expressed genes analyses were utilized to detect stromal-and immune-related genes. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was utilized for additional gene selection. The genes that were selected were utilized as the input for a stepwise regression to construct a TIME-related risk score (TIMErisk), which was then validated in Gene Expression Omnibus (GEO) database. For the evaluation of the protein expression levels of TIME regulators, the Human Protein Atlas (HPA) dataset was utilized, and for their biological functions, the TIMER and CIBERSORT algorithm, immunoreactivity, and Immune Cell Abundance Identifier (ImmuCellAI) were used. Possible OC medications were forecasted utilizing the Genomics of Drug Sensitivity in Cancer (GDSC) database and connectivity map (CMap). TIMErisk was developed based on ALPK2, CPA3, PTGER3, CTHRC1, PLA2G2D, CXCL11, and ZNF683. High TIMErisk was recognized as a poor factor for survival in the GEO and TCGA databases; subgroup analysis with FIGO stage, grade, lymphatic and venous invasion, debulking, and tumor site also indicated similar results. Functional immune cells corresponded to more incisive immune reactions, including secretion of chemokines and interleukins, natural killer cell cytotoxicity, TNF signaling pathway, and infiltration of activated NK cells, eosinophils, and neutrophils in patients with low TIMErisk. Several small molecular medications which may enhance the prognosis of patients in the TIMErisk subgroup were identified. Lastly, an enhanced predictive performance nomogram was constructed by compounding TIMErisk with the FIGO stage and debulking.ConclusionThese findings may offer a valuable indicator for clinical stratification management and personalized therapeutic options for OC patients and may be a foundation for future mechanistic research of their association.

scholarly journals RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Lan-Xin Mu ◽  
You-Cheng Shao ◽  
Lei Wei ◽  
Fang-Fang Chen ◽  
Jing-Wei Zhang
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Risk Model ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Immune Microenvironment ◽  
Model Based ◽  
Tumor Immune Microenvironment

Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors.Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups.Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient’s T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p < 0.001) and m6aRiskscore (p < 0.001) are both risk factors for breast cancer in the multivariate regression.Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.

scholarly journals The Efficacy of Risk Score System Establishment and Methylprednisolone Stratification Treatment for Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Retrospective (development) and a Prospective (validation) Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4501-4501
Author(s):  
Xiaoyu Zhu ◽  
Jiang Zhu ◽  
Baolin Tang ◽  
Kaidi Song ◽  
Linlin Jin ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Scoring System ◽  
Cord Blood Transplantation ◽  
High Risk Factors ◽  
Risk Scoring ◽  
Risk Scoring System ◽  
Different Doses

Introduction Pre-engraftment syndrome (PES) is a common immune reaction prior to neutrophil engraftment after unrelated cord blood transplantation (UCBT), with a unique clinical manifestation of non-infectious fever and skin rash. The reported incidence of PES ranges from 20% to 78%. Although many researchers believe that PES is associated with a high incidence of acute graft-versus-host disease (GVHD) but not with transplant-related mortality (TRM) , relapse, or overall survival (OS), they did not stratify the risk factors of PES, and how to carry out different doses of methylprednisolone (MP) stratified intervention therapy still remains unknown. Method s First, 136 hematological malignancy patients treated with UCBT from April 2000 to February 2012 in our transplantation center were retrospectively analysis. Among them, 92 patients occurred PES. High-risk factors for 180-day TRM in PES patients were established by univariate and multivariate analysis. Then, from January 2013 to August 2016, 221 PES patients were scored according to the risk scoring system and stratified treated with different doses of MP. Finally, in order to validate the efficacy of MP stratification treatment, we conducted a prospective, open label and non-randomized clinical trial including 240 PES patients who underwent UCBT from September 2016 to December 2018. This trial is registered at www.chictr.org.cn as ChiCTR-ONC-16009013. Results The cumulative incidence of neutrophil and platelet engraftment was significantly higher in PES group than non-PES group (97.8% vs 70.5%, P<0.001; 75.0% vs 54.5%, P=0.05). In 92 PES patients, multivariate analysis showed that failed MP treatment, multiple clinical symptoms and early onset of PES were independent high risk factors affecting180-day TRM. One high risk factor was scored as 1. The 92 PES patients were divided into PES-0, PES-1,PES-2 and PES-3, and the higher the score, the higher the TRM (17.7% vs 21.9% vs 62.5% vs 100%,respectively; P<0.001), and the lower the OS (68.3% vs 56.2% vs 25.0% vs 0%, respectively; P<0.001). Then, from January 2013 to August 2016, 221 PES patients were scored as PES-0, PES-1 and PES-2 according to the following two high risk factors (multiple clinical symptoms and early onset of PES) and stratified treated with different doses of MP (0.5mg/kg/d for PES-0, 1mg/kg/d for PES-1 and 2mg/kg/d for PES-2). Compared to the previous PES patients with the same risk score, the 180-day TRM of PES-1 and PES-2 patients was significantly reduced and the OS, disease free survival (DFS), and GVHD-free and Relapse-free survival (GRFS) were significantly increased after stratified treatment. The results in the prospective trial were similar to the retrospective study. In addition, although stratified therapy could significantly improve the prognosis of PES-2 patients cohort, the cumulative incidence of acute GVHD and GRFS are still the worst compared with other risk score patients. Therefore, how to improve the outcomes of PES-2 patients remains to be further studied. Conclusion s PES after UCBT is benefit for engraftment, but should be graded according the risk scoring system. Different doses of MP stratified intervention therapy can significantly improve the prognosis of severe PES patients. The risk scoring system of PES after UCBT and MP stratification treatment are worthy of clinical application. But the cumulative incidence of acute GVHD and GRFS in severe PES patients still need to be ameliorated in the further study. Disclosures No relevant conflicts of interest to declare.

scholarly journals Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Li ◽  
Jina Zheng ◽  
Chanjuan Gong ◽  
Kengfu Lan ◽  
Yuqing Shen ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Profile Data ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Cerna Network ◽  
Inflammatory Damage ◽  
Competing Endogenous Rnas ◽  
Immune Related Genes ◽  
Important Significance

Abstract Background Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631. Methods In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis. Results In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003). Conclusions Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

A risk scoring system for African-American (AA) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line abiraterone (ABA) or enzalutamide (ENZ).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 51-51
Author(s):  
Jacqueline T Brown ◽  
Yuan Liu ◽  
Jennifer Ann LaFollette ◽  
Omer Kucuk ◽  
Melvin R. Moore ◽  
...  
Keyword(s):  
Risk Score ◽  
Scoring System ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Grade Group ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Response ◽  
Risk Scoring ◽  
Risk Scoring System

51 Background: AA pts represented < 3% of the COU-AA-302 and PREVAIL trial cohorts that led to the approval of ABA and ENZ in the 1st line treatment of mCRPC. We characterized the clinical outcomes (CO) and developed a risk score for AA pts with mCRPC on these agents. Methods: We retrospectively reviewed 77 AA pts with mCRPC treated with 1st line ABA or ENZ at Grady Memorial Hospital from 2015-2018. The CO included median overall survival (mOS), progression-free survival (mPFS) and PSA response (PSAr) as defined by a ≥ 50% drop in PSA over the 1st 12 weeks of treatment. Cox proportional hazard model and Kaplan-Meier method were used for association with OS and PFS and logistic regression model for PSAr. The risk score was built by regression coefficient-based scoring system using OS as the 1° outcome. Covariates included grade group (GG), baseline (bl) PSA, albumin, and BMI, ECOG status, and age. Results: Median age was 60 years with median follow-up of 11.5 months (mos). 50 pts received ABA; 27 received ENZ. The overall mOS was 45.7 mos, mPFS was 12.9 mos, and PSAr was 84.4%. CO did not differ significantly for ABA vs. ENZ with a 24-month OS of 66.6% vs. 57.7% and PFS of 34.3% vs. 45%. 1 point was assigned for each of the following: GG > 3, bl PSA ≥ 108, or bl albumin ≤ 4.2. The total was classified into low (0-1), intermediate (2), and high (3) risk and associated with CO via univariate (UVA) and multivariate (MVA) analyses (Table). Conclusions: We present the efficacy of ABA and ENZ in a cohort of AA pts with mCRPC. Risk grouping using bl PSA, bl albumin and GG may predict CO in this population. These results should be validated in a larger, prospective study.[Table: see text]

scholarly journals Identification of Genomic Instability Related Lncrna Signature Associated with Immune Microenvironment in Pancreatic Cancer

2021 ◽  
Author(s):  
Xiaole Zhu ◽  
Rong Yu ◽  
Yunpeng Peng ◽  
Chaoqun Hou ◽  
Chenyuan Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Genomic Instability ◽  
Risk Score ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Immune Microenvironment ◽  
Important Indicator ◽  
Cox Regression Analysis ◽  
Tumor Immune Microenvironment

Abstract Background: Increasing evidence suggested that the critical roles for lncRNAs in the maintenance of genomic stability. However, the identification of genomic instability related lncRNA signature (GILncSig) and their clinical significance in tumor immune microenvironment of pancreatic cancer remain largely unexplored.Methods: In the present study, a systematic analysis of lncRNA expression profiles and somatic mutation profiles was performed in pancreatic cancer patients from TCGA. We performed co-expression network and Gene Ontology (GO) enrichment analyses to determine the potential functions and pathways involved in lncRNAs are associated with genomic instability. We then development a risk score model to describe the characteristics of the model and verify its prediction accuracy. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in pancreatic cancer. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. Results: We identified 206 GILncSig, of which five were screened to develop a prognostic GInLncSig model. Multivariate Cox regression analysis and stratified analysis revealed that the prognostic value of the GILncSig was independent of other clinical variables. ROC analysis suggested that GILncSig is better than the existing lncRNA-related signatures in predicting survival. Additionally, the prognostic performance of the GILncSig was also found to be favorable in patients carrying wild-type KRAS, TP53 and SMAD4. Besides, a nomogram exhibited appreciable reliability for clinical application in predicting the prognosis of patients. Finally, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4, etc.). Conclusion: In summary, the GILncSig identified by us may have crucial role in immune cell infiltration，immunotherapy and important indicator for clinical stratification management and therapy decisions for pancreatic cancer patients.

scholarly journals Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis

2020 ◽  
Author(s):  
Yang Li ◽  
Ji Na Zheng ◽  
Chan Juan Gong ◽  
Keng Fu Lan ◽  
Yu Qing Shen ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Profile Data ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Cerna Network ◽  
Inflammatory Damage ◽  
Competing Endogenous Rnas ◽  
Immune Related Genes ◽  
Important Significance

Abstract Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631.Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis.Results: In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003).Conclusions: Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

scholarly journals A Ferroptosis-Related Signature Robustly Predicts Clinical Outcomes and Associates With Immune Microenvironment for Thyroid Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Mingqin Ge ◽  
Jie Niu ◽  
Ping Hu ◽  
Aihua Tong ◽  
Yan Dai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
Low Risk ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Immune Microenvironment ◽  
Cox Regression Analysis

Objective: This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment.Methods: Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated via multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted via GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR.Results: A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score (p = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis (p = 0.015, HR: 1.870, 95%CI: 1.132–3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues.Conclusion: Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.

scholarly journals Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Shang Xie ◽  
Xin-Yuan Zhang ◽  
Xiao-Feng Shan ◽  
Vicky Yau ◽  
Jian-Yun Zhang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Treatment Planning ◽  
Immune Cell ◽  
Imaging System ◽  
Individual Treatment ◽  
Immune Microenvironment ◽  
Node Metastasis ◽  
Tumor Immune Microenvironment ◽  
Formalin Fixed Paraffin Embedded

Background. Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. Methods. We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. Results. Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. Conclusion. The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.

scholarly journals Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1796 ◽  
Author(s):  
Chengbiao Chu ◽  
Kai Yao ◽  
Jiangli Lu ◽  
Yijun Zhang ◽  
Keming Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Granzyme B ◽  
Expression Patterns ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8+ or Granzyme B+ T cells, FOXP3+ regulatory T cells, and CD68+ or CD206+ macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV–positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV–negative tumors (p = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.

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