scholarly journals Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome

2021 ◽  
Author(s):  
Katie E. Blise ◽  
Shamilene Sivagnanam ◽  
Grace L. Banik ◽  
Lisa M. Coussens ◽  
Jeremy Goecks

ABSTRACTRecent research has provided compelling evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors correlates with survival and response to therapy in numerous cancer types. Here, we report results of a quantitative single-cell spatial analysis of the TiME of primary and recurrent human head and neck squamous cell carcinoma (HNSCC) tumors, that builds upon our initial longitudinal study of these same HNSCCs that annotated immune complexity at near single cell resolution. Herein, we extended multiple spatial algorithms to quantify spatial landscapes of immune cells within TiMEs. Most notably, we report that spatial compartmentalization, rather than mixing, between neoplastic tumor cells and immune cells is associated with longer patient survival, as well as revealing mesenchymal spatial cellular neighborhoods and their association with improved patient outcomes. Results reported herein are concordant with studies in other tumor types, thus indicating that cellular heterogeneity within tumors trends with spatial TiME features, and are likely prognostic for patient survival.

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 73208-73218 ◽  
Author(s):  
Andres Stucky ◽  
Parish P. Sedghizadeh ◽  
Susan Mahabady ◽  
Xuelian Chen ◽  
Cheng Zhang ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Guohong Liu ◽  
Chunjue Yuan ◽  
Jiaojiao Ma ◽  
Yunbao Pan ◽  
Haibo Xu

Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy accompanied by noted alterations in various immune cells and cytokines. Recognition of the immune system’s role in contributing to cancer development is an important advancement in our original understanding of carcinoma. We obtained HNSCC gene expression and clinical data from The Cancer Genome Atlas (TCGA) database. We assessed the relative proportion of 22 Infiltrating immune cell types in both HNSCC and adjacent non-cancer tissues using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, identifying the influence of the immune cells content in tumor staging and survival prediction. We further predicted the tumor purity, and the presence of infiltrating stromal/immune cells in HNSCC tissues using Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, identifying its potential correlation with patient survival. Stromal and immune score-associated differentially expressed genes (DEGs) were subsequently verified and their roles in immune response were displayed by functional enrichment analysis and protein-protein interaction (PPI) network. Our research demonstrated the underlying association between the immune microenvironment and HNSCC, and the results were intended to serve as valuable terms for HNSCC diagnosis, prognosis, and targeted immune therapy.


1998 ◽  
Vol 90 (11) ◽  
pp. 824-832 ◽  
Author(s):  
Jennifer Rubin Grandis ◽  
Mona F. Melhem ◽  
William E. Gooding ◽  
Roger Day ◽  
Valerie A. Holst ◽  
...  

2022 ◽  
Author(s):  
hamid abbaszadeh ◽  
Mahdieh Rajabi-Moghaddam

Abstract Advanced head and neck squamous cell carcinoma (HNSCC) is treated with radiotherapy, chemotherapy, targeted therapy or a combination of these treatments. Variations in toxicity and response to therapy are observed among patients despite similar clinicopathologic characteristics which are attributed to single nucleotide polymorphisms (SNPs). The aim of this review was to evaluate the impact of SNPs on toxicity and response to therapy in HNSCCs. A web-based search of all original articles about the impact of gene polymorphisms on toxicity and response to therapy in HNSCCs was done until September 2021 using international English language databases including Google Scholar, Scopus, PubMed and Web of science. Findings were categorized by type of treatment (radiotherapy, chemotherapy, targeted therapy, or combination therapy). In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. Among studied SNPs with probable impact on toxicity and response to therapy are XRCC1, XRCC3, RAD51, Ku70, NBN, CAT, GSTP1, GSTT1, GSTM1, XPD, XPC, ERCC1, MMP3, ACSL6, EXO1, CXP2D6, FcγRIIIa, AurkA, and EGFR. Understanding gene polymorphisms will help us move toward personalized medicine and determine which patients will actually benefit from therapies for HNSCCs. By examining the SNPs, it is possible to make predictions about the patient's response to treatment or development of toxicity after treatment, and if necessary, make changes in the patient's treatment regimen.


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