Tumor Infiltrating Lymphocytes and CD8+?T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Chatzopoulos K
PROVIDER: S-EPMC7413976 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma.
Chatzopoulos Kyriakos K Kotoula Vassiliki V Manoussou Kyriaki K Markou Konstantinos K Vlachtsis Konstantinos K Angouridakis Nikolaos N Nikolaou Angelos A Vassilakopoulou Maria M Psyrri Amanda A Fountzilas Georgios G
Head and neck pathology 20191120 3
To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm<sup>2</sup> were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm<sup>2</sup>). TIL density and CD8+ counts weakly correlated with each other (Spearman's ...[more]
Similar Datasets
Project description:Quality metrics for patients with laryngeal squamous cell carcinoma (SCC) exist, but whether compliance with these metrics correlates with improved survival is unknown.To examine whether compliance with proposed quality metrics is associated with improved survival in patients with laryngeal SCC treated with surgery with or without adjuvant therapy.This retrospective cohort study included patients from a tertiary care academic medical center who had previously untreated laryngeal SCC and underwent surgery with or without adjuvant therapy from January 1, 2003, through December 31, 2012. Data analysis was performed from August 4, 2015, through December 13, 2015.Surgery with or without adjuvant therapy.Compliance with quality metrics from the American Head and Neck Society (AHNS), National Comprehensive Cancer Network (NCCN) guidelines, and institutional metrics with face validity covering pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. The association between compliance with the group of metrics and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) was explored using Cox proportional hazards analysis. The association between compliance with individual metrics and survival was similarly determined.A total of 243 patients (184 men and 59 women) were included in the study (median age, 62 years; age range, 23-87 years). No association was found between increasing levels of compliance with the AHNS or NCCN metrics and survival. The only AHNS or NCCN metric for which greater compliance correlated with improved survival on multivariable Cox proportional hazards analysis controlling for pT stage, pN stage, extracapsular spread, margin status, and comorbidity was pretreatment multidisciplinary evaluation for patients with stage cT3-4 or cN1-3 disease (OS adjusted hazard ratio [aHR], 0.47; 95% CI, 0.24-0.94; DFS aHR, 0.45; 95% CI, 0.23-0.85). For the institutional metrics, multidisciplinary evaluation for all patients (OS aHR, 0.51; 95% CI, 0.29-0.88; DFS aHR, 0.50, 95% CI, 0.32-0.80) and elective neck dissection yield of 18 lymph nodes or more (DFS aHR, 0.36; 95% CI, 0.14-0.99) were associated with improved survival on multivariable Cox proportional hazards analysis.In this cohort of patients with surgically treated laryngeal SCC, multidisciplinary evaluation and elective neck dissection yield of 18 lymph nodes or more are associated with improved survival. Development of better quality metrics is necessary because increased compliance with metrics described by the AHNS and NCCN is not associated with improved survival. Previously described metrics for surgically treated oral cavity cancer are not prognostic for surgically treated laryngeal SCC. Future multi-institutional collaboration will be required to validate these findings, develop better quality metrics, and evaluate whether quality metrics for head and neck cancer are site specific.
| S-EPMC6086577 | biostudies-literature
Project description:ObjectivesLaryngeal squamous cell carcinomas (LSCCs) typically have an excellent prognosis for stage I tumors but a significant risk of locoregional and distant recurrence for intermediate to advanced disease. This study will investigate the clinical relevance of the tumor microenvironment in a large cohort of treatment-naïve patients affected by stage II-IV LSCC.MethodsWhole slide-based digital pathology analysis was applied to measure six immune cell populations identified by immunohistochemistry (IHC) staining for CD3, CD8, CD20, CD66b, CD163 and CD38. Survival analysis was performed by Cox proportional hazards models and unsupervised hierarchical clustering using the k-means method. Double IHC staining and in-situ hybridisation by RNAscope allowed further analysis of a protumoral B cell population.ResultsA cohort of 98 patients was enrolled and analysed. The cluster of immune-infiltrated LSCCs demonstrated a significantly worse disease-specific survival rate. We also discovered a new association between high CD20+ B cells and a greater risk of distant recurrence. The phenotypic analysis of infiltrating CD20+ B cells showed a naïve (BCL6-CD27-Mum1-) regulatory phenotype, producing TGFβ but not IL10, according to an active TGFβ pathway, as proved by positive pSMAD2 staining.ConclusionThe identification of regulatory B cells in the context of LSCC, along with the activation of the TGFβ pathway, could provide the basis for new trials investigating the efficacy of already available molecules targeting the TGFβ pathway in the treatment of LSCC.
| S-EPMC10131296 | biostudies-literature
Project description:Objectives/hypothesisTo assess the disease control, survival rates, and prognostic factors of exclusive surgical treatment for patients with pT3 N0 laryngeal squamous cell carcinoma (LSCC).Study designMulticentric retrospective cohort study.MethodsMulticentric retrospective case series of previously untreated patients with pT3 R0N0 LSCC, who received exclusive surgery between 2011 and 2019. Tumor location; subsite involvement; grading; and lymphatic, vascular, and perineural invasion were reported. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were measured.ResultsFifty-four patients (mean age 67.1; male sex 83.3%; mean follow-up period 37 months) underwent total laryngectomy (48.1%) or partial laryngectomy (51.9%). Ipsilateral or bilateral neck dissection was performed in 46 (85.2%) cases. Perineural invasion was more frequent in case of supraglottic involvement than glottic involvement (85.7% vs. 14.3%, P = .03). Five (9.3%) patients experienced recurrence (3 local recurrences, 1 nodal recurrence, 1 distant recurrence). Rate of recurrence differed between glottic (0%), supraglottic (80%), and transglottic (20%) tumors (P = .01), with a lower risk yielded by glottic involvement (odds ratio [OR], 0.05, 95% confidence interval [95% CI], 0.01-0.56, P = .01). A higher risk was recorded in case of perineural invasion (OR, 66.0, 95% CI, 1.41-3085.3, P = .03). The OS, DSS, and DFS were 79.6%, 96.3%, and 90.7%, without differences regarding the type of surgery. The DFS was lower in case of supraglottic involvement when compared to purely glottic LSCC (83.9% vs. 100%, P = 0.02).ConclusionsExclusive surgery is a safe option for patients with pT3 R0N0 LSCC. Adjuvant treatments or closer follow-up monitoring might be considered in case of supraglottic involvement or perineural invasion.Level of evidence4 Laryngoscope, 131:2262-2268, 2021.
| S-EPMC8518991 | biostudies-literature
Project description:The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36-0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34-0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4-0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34-0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16-0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10-0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome.
| S-EPMC8145951 | biostudies-literature
Project description:Purpose:The presence of CD8+ tumor-infiltrating lymphocytes (TILs) has been reported to be associated with treatment outcomes in many types of solid tumors. However, the results vary due to the various methods of visual estimation and subjective interpretation. The current study is the first to use digital image analyses to evaluate the density of CD8+/CD3+ TILs in tongue squamous cell carcinoma (TSCC). Patients and Methods:From 2005 to 2015, a cohort of 258 TSCC patients were consecutively enrolled in this study. After immunohistochemistry on representative sections, the density of CD8+/CD3+ TILs at tumor invasive margins was evaluated by digital image analysis. The subjects were stratified by the median values of CD3+ cell density, CD8+ cell density, CD8/CD3, and scores (0, 1, and 2) to demonstrate the association with various clinicopathological manifestations. Results:Low CD8+ TIL counts were associated with advanced tumor stages (p=0.034), and low CD8/CD3 ratios were associated with perineural invasion (p=0.043). Both parameters were also associated with increased tumor depths (p=0.034 and 0.004, respectively). Univariate analyses revealed that advanced tumor stages, perineural invasion, extranodal extension, tumor depth, lower CD8 counts, and lower scores (score 0 vs 2) were associated with poorer overall survival, and multivariate analysis further indicated that extranodal extension and low scores (score 0 vs 2) were both independent factors for overall survival (p < 0.0001 and p = 0.0369, respectively). Conclusion:The use of digital image analysis to assess CD8+ TILs at the invasive margins provides an objective indicator of prognoses including overall survival.
| S-EPMC7490039 | biostudies-literature
Project description:The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune-cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and IBA-1, and analyzed an average of 15,000 cells per sample. Classifying tumors as either high (>30%) or low (<30%) TILs, we found that increased TILs density correlated with survival. Phenotyping these TILs we found tumors with low TILs had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p < 0.01) as well as in their microenvironment (p < 0.001). Contrastingly, the tumors with high TILs displayed higher levels of microglia, as measured by IBA-1 expression. Low TILs-tumors displayed CD8+ T-cells that co-express VISTA (p < 0.01) significantly more compared to high TILs group, where CD8+cells significantly co-express IBA-11 (p < 0.05). These results were supported by RNA analysis of a publicly available, independent cohort. Our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.
| S-EPMC8150725 | biostudies-literature
Project description:Background: Tumor-infiltrating lymphocytes (TILs) play a role in the anti-tumor immune response, and are often found in esophageal squamous cell carcinoma (ESCC). Methods: We performed a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes of TILs based on their abundance and infiltrating location. A literature search of PubMed/Medline, Embase, Web of Science and the Cochrane Library was conducted. Studies that investigated the prognostic significance of generalized, CD8+, CD4+, FoxP3+, CD3+, and CD45O+ TILs in ESCC patients were included. Results: In pooled analysis, generalized TILs infiltrating the entire tumor mass were positively associated with disease-free survival (DFS), with a univariate-related hazard ratio (HR) of 0.630 [95% confidence interval (CI) 0.415-0.955], and also positively associated with overall survival (OS), with a univariate-related HR of 0.586 (0.447-0.770) and a multivariate-related HR of 0.621 (0.439-0.878). The pan-tumor, intra-tumor and peri-tumor CD8+ TILs had a favorable effect on OS, with univariate-related HRs of 0.733 (0.555-0.968), 0.797 (0.660-0.962), and 0.776 (0.635-0.948), respectively. Similar results were observed in CD8+ TILs that infiltrated the whole tumor mass, with a multivariate-related HR of 0.705 (0.524-0.947). CD4+, FoxP3+, CD3+, and CD45O+ TILs were not linked to DFS or OS. Subtypes and spatial locations of TILs seemed to influence study outcomes. Conclusions: Experimental and analytical methods of future studies should be carefully designed to avoid overestimating the effect of TILs on prognosis. Our meta-analysis confirms the prognostic efficacy of generalized TILs and CD8+ TILs in esophageal squamous cell carcinoma (ESCC) patients.
| S-EPMC7198736 | biostudies-literature
Project description:It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head and neck squamous cell carcinoma (HNSCC). PubMed, Cochrane, Embase, Scopus, and Web of Science were searched up to September 2020. This study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Risk ratios from individual studies were displayed in forest plots and the pooled hazard ratios (HR) of death and corresponding confidence intervals (CI) were calculated according to random-effects models. Risk of bias of the included studies was assessed through the Newcastle-Ottawa scale. 28 studies met the inclusion criteria. Studies conducted on HNSCC subsites combined reported a significant reduction in the risk of death for both high CD4+ (HR: 0.77; 95% CI: 0.65-0.93) and high CD8+ TILs (HR: 0.64; 95% CI: 0.47-0.88). High CD4+ TILs were associated with significantly better overall survival among oropharyngeal HNSCC (HR: 0.52; 95% CI: 0.31-0.89), as well as high CD8+ TILS in Human papillomavirus -ve and +ve cancers (HR: 0.39; 95% CI: 0.16-0.93 and HR: 0.40; 95% CI 0.21-0.76 respectively). CD8+ TILs were also associated with improved survival in hypopharyngeal cancers (HR = 0.43 CI: 0.30-0.63). No significant association emerged for patients with cancer of the oral cavity or larynx. The findings from this meta-analysis demonstrate the prognostic significance of CD8+ and CD4+ TILs in HNSCC and variation in tumor subsite warrants further focused investigation. We highlight how TILs may serve as predictive biomarkers to risk stratify patients into treatment groups, with applications in immune-checkpoint inhibitors notable areas for further research.
| S-EPMC7918220 | biostudies-literature
Project description:ObjectiveBioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm.Study designRetrospective study.SettingTertiary care hospital.MethodsPatients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM).ResultsAfter controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response (P = .012).ConclusionThese findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.
| S-EPMC8613299 | biostudies-literature
Project description:BACKGROUND:Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. METHODS:Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. RESULTS:High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p?=?0.0014; DSS hazard ratio: 0.09, p?=?0.0015; DFS hazard ratio: 0.18, p?=?0.0018) in recurrent/persistent LSCC. CONCLUSIONS:An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.
| S-EPMC6375747 | biostudies-literature