Importance of the immune system in head and neck cancer

Mirza, Adal H.; Thomas, Gareth J.; Ottensmeier, Christian; King, Emma V.

doi:10.1002/hed.25716

Cited by 33 publications

(27 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene expression signatures for survival stratification in HNSCC patients have been proposed by various studies. Elements of the immune system, such as the tumor immune evading mechanism, are increasingly recognized crucial in HNSCC progression [7][8][9]. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PDL-1) complex is part of an important immunecheckpoint which is involved in antitumor activity [10].…”

Section: Introductionmentioning

confidence: 99%

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

She

Kong

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. Methods: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. Results: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01). Conclusion: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

show abstract

Section: Introductionmentioning

confidence: 99%

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

She

Kong

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…Different mechanisms of tumor immune evasion have been described in HNSCC, and various immune checkpoints are found overexpressed in the surrounding tumor microenvironment to induce the exhaustion of effector T cells, being the PD-1/PD-L1 the most extensively studied [4,17]. In marked contrast, only few studies have so far investigated the role of LLT1/NKRP1(CD161) inhibitory checkpoint in cancer.…”

Section: Discussionmentioning

confidence: 99%

Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma

et al. 2020

View full text Add to dashboard Cite

Lectin-like transcript 1 (LLT1) expression by tumor cells contributes to immune evasion, thereby emerging as a natural killer (NK) cell-mediated immunotherapeutic target. This study is the first to investigate LLT1 expression (encoded by CLEC2D gene) in head and neck cancers to ascertain its impact on patient prognosis. LLT1 expression was analyzed by immunohistochemistry in a homogeneous cohort of human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinomas (OPSCC), and correlated with clinical data. Results were further validated using transcriptomic data from the TCGA database. Tumoral LLT1 expression was detected in 190/221 (86%) OPSCC specimens, whereas normal pharyngeal epithelium was negative. Patients harboring LLT1-positive tumors showed significantly lower disease-specific (DSS) and overall survival (OS) (p = 0.049 and p = 0.036, respectively, log-rank test). High density of LLT1-positive tumor-infiltrating lymphocytes (TIL) was also frequently detected in 160 (73%) OPSCC samples, and significantly associated with better DSS and OS (p < 0.001 and p = 0.007, respectively). Multivariate Cox analysis further revealed that tumoral LLT1 expression and infiltration of LLT1-positive TIL were independent prognostic factors for DSS and OS. CLEC2D mRNA levels are also significantly increased in primary tumors compared to normal tissue. Strikingly, the prognostic impact of CLEC2D mRNA levels varied depending on HPV status in OPSCC, and among distinct cancer types. CLEC2D expression was significantly correlated with NK cell infiltration using the MCP-counter model. These findings uncover LLT1/CLEC2D as an independent prognostic factor in HPV-negative OPSCC, and a potential novel target for immunotherapy.

show abstract

“…The immune system is known to be significantly involved in HNSCC progression [5][6][7], and anti-programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have been approved to treat recurrent and/or metastatic HNSCCs that are refractory to platinum therapy [8,9]. Several immune-biomarkers have been highlighted as useful prognostic indicators for HNSCC [10][11][12][13]; for instance, circulating CD8 + T cell levels prior to treatment have been found to be associated with improved survival in patients with advanced oropharyngeal cancer [10], while high tumor-infiltrating lymphocyte levels are related with increased overall survival (OS) [11], and increased CD68 + macrophage counts in oral squamous cell carcinoma are known to be significantly correlated with mortality [12].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of CD200R1 mRNA Expression in Head and Neck Squamous Cell Carcinoma

Chang

Lee

et al. 2020

Cancers

View full text Add to dashboard Cite

Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes (CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.

show abstract

Importance of the immune system in head and neck cancer

Cited by 33 publications

References 89 publications

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma

Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma

Prognostic Value of CD200R1 mRNA Expression in Head and Neck Squamous Cell Carcinoma

Contact Info

Product

Resources

About