scholarly journals Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Kanako Yoshimura ◽  
Takahiro Tsujikawa ◽  
Junichi Mitsuda ◽  
Hiroshi Ogi ◽  
Sumiyo Saburi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
High Density ◽  
Helper T Cells ◽  
Tissue Segmentation ◽  
Immune Microenvironment

BackgroundFunctional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC).MethodsA total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma.ResultsTissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases.ConclusionThis study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.

scholarly journals The Functionalities and Clinical Significance of Tumor-Infiltrating Immune Cells in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jishuai Zhang ◽  
Haifeng Wang ◽  
Haitao Wu ◽  
Guangliang Qiang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Natural Killer ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Immune Cells ◽  
Gene Set Enrichment Analysis

Tumor-infiltrating immune cells have been implicated in the tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). However, the functionalities and clinical significance of immune cells remain largely unveiled. In this study, the gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were extracted. The relative infiltrating levels were estimated by single-sample gene set enrichment analysis. Some cytotoxic immune cells were attenuated, and resting cytotoxic immune cells were accumulated in ESCC. Remarkably, we also observed that infiltrating levels of macrophage M2 and resting natural killer (NK) cells were increased in nonresponders of CRT, and T cells that had anticancer activities such as activated memory CD4 and T helper 2 (Th2) cells were significantly reduced in ESCC tissues of the nonresponders. Moreover, the high infiltrations of the resting natural killer (NK) and dendritic cell (DC) were observed to result in a shorter overall survival in ESCC. Consistently, high expression of immune checkpoint genes, CTLA4 and HAVCR2, was associated with poor prognosis. Furthermore, STAT5B, a key transcription factor, as well as its target genes, involved in the regulation of T cells, was significantly downregulated in ESCC, especially subgroup I, indicating that downregulation of STAT5B might be associated with reduced T cell-mediated anticancer activity. In conclusion, the present study significantly improved our understanding of the regulatory roles of immune cells in ESCC.

Tumor immune microenvironment alterations in penile squamous cell carcinoma using multiplex immunofluorescence and image analysis approaches.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Jad Chahoud ◽  
Frederico Netto ◽  
Rossana Lazcano Segura ◽  
Edwin Roger Parra Cuentas ◽  
Xin Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Image Analysis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lower Risk ◽  
Cytotoxic T Cells ◽  
T Cell Subsets ◽  
Immune Microenvironment ◽  
Penile Squamous Cell Carcinoma

4 Background: Penile Squamous Cell Carcinoma (PSCC) is a rare but often fatal disease. In this study, we characterize the poorly understood immune microenvironment using multiplex immunofluorescence (mIF) and image analysis approaches in 54 patients with PSCC. Methods: Representative blocks of 54 PSCC patients were stained for six immune markers: CD3, CD8, CD68, PD-1, PD-L1, Pancytokeratin and DAPI. Two experienced pathologists using an image analysis system (InForm 2.2.4) divided them into the tumor and stroma compartment and assessed the different densities of cell phenotypes using R studio with results expressed as cells/mm2. The statistical correlations were performed using Fisher’s exact test, Pearson and Log-rank test for Kaplan Meyer plots. Results: 54 patients with confirmed diagnosis of PSCC had a median age of 62 (IQR 50-70). All samples were from the primary penile tumor with the majority of cases being HPV(–) (62%). We observed significantly higher stromal cytotoxic T cells in HPV(+) cases compared to HPV(–) ( P=0.04). Using the mean macrophage count as cutoff for positivity, high densities of total tumor macrophages CD68+ were associated with significantly improved estimated median cancer specific survival (CSS) (NA, P=0.04), median overall survival (OS) (68mos vs NA P=0.02) and lower risk of regional recurrence ( P=0.04). On the other hand, the high densities of stromal cytotoxic T cells antigen-experienced (CD3+CD8+PD-1+), was associated with significantly worse median OS (27 vs 102mos P=0.05) and median disease free survival (DFS) (18.2mos vs NA P= 0.07). Also, high densities of stromal T cells antigen-experienced (CD3+PDL-1+), were associated with significantly better CSS (NA, P=0.06) and better median OS (142.1 vs 68.8mos P=0.14). Conclusions: Using novel multiplex image analysis to assess the immune microenvironment in primary PSCC, we showed that high macrophage levels were associated with lower risk of recurrence and improved survival outcomes. Moreover, a low level of exhausted stromal cytotoxic PD-1+ T cells was associated with improved PSCC survival. Further characterization of T cell subsets in relation to tumor HPV status is ongoing.

scholarly journals Influence of Immune Microenvironment on Diagnosis and Prognosis of Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Guohong Liu ◽  
Chunjue Yuan ◽  
Jiaojiao Ma ◽  
Yunbao Pan ◽  
Haibo Xu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cells ◽  
Relative Proportion ◽  
Neck Squamous Cell Carcinoma ◽  
Functional Enrichment ◽  
Survival Prediction ◽  
Immune Microenvironment

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.

scholarly journals Prognostic Potential of Tumor-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2268
Author(s):  
Ana Caruntu ◽  
Liliana Moraru ◽  
Mihai Lupu ◽  
Florina Vasilescu ◽  
Marius Dumitrescu ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Prognostic Role ◽  
Immune Microenvironment ◽  
Improved Outcome

(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.

scholarly journals Interleukin 32 Promotes Foxp3+ Treg Cell Development and CD8+ T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Han ◽  
Shiyu Chen ◽  
Zheyi Chen ◽  
Bingqian Zhou ◽  
Yingxia Zheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Treg Cells ◽  
Sequencing Data

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4+ regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels. Knocking down of IL-32 reduced Foxp3 and interferon gamma (IFNγ) expressions in CD4+ and CD8+ T cells, respectively. IL-32 was positively correlated with Foxp3, IFNG, and GZMB expression but was negatively correlated with proliferation score. IL-32 may have a contradictory role in the TME such as it promotes IFNγ expression in CD8+ T cells, which enhances the antitumor activity, but at the same time induces Foxp3 expression in CD4+ T cells, which suppresses the tumor immune response. Our results demonstrate different roles of IL-32 in Treg cells and CD8+ T cells and suggest that it can potentially be a target for ESCC cancer immunosuppressive therapy.

scholarly journals Relationship between the immune microenvironment of different locations in a primary tumour and clinical outcomes of oesophageal squamous cell carcinoma

2019 ◽  
Vol 122 (3) ◽  
pp. 413-420 ◽  
Author(s):  
Ken Hatogai ◽  
Satoshi Fujii ◽  
Shigehisa Kitano ◽  
Takashi Kojima ◽  
Hiroyuki Daiko ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Immune Status ◽  
Primary Tumour ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Invasive Front ◽  
Immune Microenvironment

Abstract Background Tumour microenvironments can differ according to intratumoural locations. We investigated the immune status at different locations in primary tumours and its clinical significance in oesophageal squamous cell carcinoma (ESCC). Methods The number of CD8+ tumour-infiltrating immune cells (TIICs) and PD-1+ TIICs, and PD-L1 expression on tumour cells (PD-L1TC) were immunohistochemically examined in the surface (Surf), centre (Cent) and invasive front (Inv) of tumours surgically resected from 192 patients with ESCC. Results The PD-L1+ rate was lower in Inv than in Cent (12.0% vs. 18.2%, P = 0.012), although the numbers of CD8+ TIICs and PD-1+ TIICs were comparable among intratumoural locations. High numbers of CD8+ and PD-1+ TIICs and positive PD-L1TC were related to better overall survival (OS) only in Surf and Cent (CD8: P = 0.012 in Surf, 0.018 in Cent, and 0.165 in Inv; PD-1: P = 0.028 in Surf, 0.021 in Cent, and 0.208 in Inv; and PD-L1: 0.044 in Surf, 0.026 in Cent, and 0.718 in Inv). Positive PD-L1TC in Surf and/or Cent but not in Inv demonstrated a strong tendency toward better OS (P = 0.053). Conclusions Immune microenvironments according to the intratumoural location have different effects on the survival of patients with ESCC.

scholarly journals CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei-Jie Tian ◽  
Peng-Hui Feng ◽  
Jun Wang ◽  
Ting Yan ◽  
Qing-Feng Qin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cells ◽  
Cervical Squamous Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis ◽  
Positive Correlation

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.

scholarly journals Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Takumi Kumai ◽  
Takayuki Ohkuri ◽  
Toshihiro Nagato ◽  
Yoshinari Matsuda ◽  
Kensuke Oikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Helper T Cells
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