Dataset Information

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: (1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

SUBMITTER: Parikh AS

PROVIDER: S-EPMC10571517 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

Parikh Anuraag S AS Li Yize Y Mazul Angela A Yu Victoria X VX Thorstad Wade W Rich Jason J Paniello Randal C RC Caruana Salvatore M SM Troob Scott H SH Jackson Ryan S RS Pipkorn Patrik P Zolkind Paul P Qi Zongtai Z Adkins Douglas D Ding Li L Puram Sidharth V SV

Cancers 20231005 19

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes fro ...[more]

PMID: 37835549

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Project description:Background: Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time. Methods: Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB. Results: In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels. Conclusion: HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.

Project description:For TP53-mutated head and neck squamous cell carcinomas (HNSCCs), the codon and specific amino acid sequence change resulting from a patient's mutation can be prognostic. Thus, developing a framework to predict patient survival for specific mutations in TP53 would be valuable. There are many bioinformatics and functional methods for predicting the phenotypic impact of genetic variation, but their overall clinical value remains unclear. Here, we assess the ability of 15 different methods to predict HNSCC patient survival from TP53 mutation, using TP53 mutation and clinical data from patients enrolled in E4393 by the Eastern Cooperative Oncology Group (ECOG), which investigated whether TP53 mutations in surgical margins were predictive of disease recurrence. These methods include: server-based computational tools SIFT, PolyPhen-2, and Align-GVGD; our in-house POSE and VEST algorithms; the rules devised in Poeta et al. with and without considerations for splice-site mutations; location of mutation in the DNA-bound TP53 protein structure; and a functional assay measuring WAF1 transactivation in TP53-mutated yeast. We assessed method performance using overall survival (OS) and progression-free survival (PFS) from 420 HNSCC patients, of whom 224 had TP53 mutations. Each mutation was categorized as "disruptive" or "non-disruptive". For each method, we compared the outcome between the disruptive group vs. the non-disruptive group. The rules devised by Poeta et al. with or without our splice-site modification were observed to be superior to others. While the differences in OS (disruptive vs. non-disruptive) appear to be marginally significant (Poeta rules + splice rules, P = 0.089; Poeta rules, P = 0.053), both algorithms identified the disruptive group as having significantly worse PFS outcome (Poeta rules + splice rules, P = 0.011; Poeta rules, P = 0.027). In general, prognostic performance was low among assessed methods. Further studies are required to develop and validate methods that can predict functional and clinical significance of TP53 mutations in HNSCC patients.

Dataset Information

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

Publications

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

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