Prognostic significance of tumor-infiltrating lymphocytes in patients with operable tongue cancer

Chen, Wan‐Yu; Wu, Chengyuan; Wang, Chunwei; Lan, Keng-Hsueh; Liang, Hongyin; Huang, Bing‐Shen; Chang, Yih‐Leong; Kuo, Sung‐Hsin; Cheng, Ann‐Lii

doi:10.1186/s13014-018-1099-6

Cited by 27 publications

(24 citation statements)

References 27 publications

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“…This finding confirms and underlines the well-known antitumoral effect of CD8 + T killer cells, which was observed in several solid cancers (23,24,40,(65)(66)(67). As previously shown by Chen (39) and now validated by our data, in OSCC, not only infiltration density of TIL subsets but also ratio of TILs, particularly CD8s:CD4s ratio, is of crucial impact in patient outcome and could potentially be taken into account when considering patient prognostication and treatment stratification.…”

Section: Discussionsupporting

confidence: 90%

“…40). Especially in OSCC, a cancer exposed to an extensive microbial environment and noxae such as tobacco and alcohol within the oral cavity, Tregs potentially may inhibit harmful protumoral chronic inflammation (39,59). A hint to this explanation might be that in our cohort, stromal localization of Tregs was correlated with outcome.…”

Section: Discussionmentioning

confidence: 81%

“…As reviewed in Refs. 26,27,39, and 40, in oral cancer, the prognostic impact of FOXP3 + Tregs is, up to date, controversial in the majority of studies, including ours (analyzing the largest patient cohort), linking Tregs to a favorable outcome contrasted by a few others, which found a negative correlation (which was, however, only determined by univariate statistical analysis). Furthermore, in addition to previous studies (60-64), our results show the impact of localization of TILs in the tumor stromal compartment as opposed by the epithelial compartment as stromal but not epithelial Tregs display an independent impact on prognosis.…”

Section: Discussionmentioning

confidence: 82%

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Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma

Boxberg

Leising

Steiger

et al. 2019

The Journal of Immunology

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Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial–mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3+/CD4+/CD8+/CD4+FOXP3+/IL-17A+) were quantified, and ratios were calculated. HLA class I in tumor cells was evaluated immunohistochemically. mRNA in situ hybridization to detect IFN-γ was performed. Analysis was performed within invasive front (IF) and tumor center (TCe). Decreased HLA expression was associated with low TIL density, pronounced stromal content, and high BA; IFN-γ in TILs was correlated with high-density TILs; and IFN-γ in tumor cells was correlated with absence of BA (p < 0.05). Heterogeneity of parameters (TCe/IF) was rare. Low density of stromal CD4+FOXP3+ TILs within TCe and IF was identified as an independent prognostic factor for poor overall, disease-specific, and disease-free survival (p ≤ 0.011). Refining prognostication in OSCC with high-density CD4+FOXP3+ infiltrate within TCe and/or IF, high FOXP3:CD4 ratio was significantly correlated with favorable outcome in this subgroup. Furthermore, high-stromal CD8:CD4 ratio was found to be an independent favorable prognostic factor. In summary, immunologic parameters were closely intertwined. Morphologic correlates of epithelial–mesenchymal transition were associated with downregulation of HLA and decreased inflammation. Heterogeneity was infrequent. Low-density stromal CD4+FOXP3+ infiltrate within TCe and IF was an independent poor prognostic factor. Stratification of cases with high-density CD4+FOXP3+ TILs by FOXP3:CD4 ratio enables refinement of prognostication of this subgroup. CD8:CD4 ratio was identified as an independent prognostic factor.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 82%

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Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma

Boxberg

Leising

Steiger

et al. 2019

The Journal of Immunology

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“…Patients with advanced stage tumors also had higher proportions of CD3 cells compared to CD4 or CD8 T cells, suggesting that progression of their disease correlated with a shift toward a more suppressive TME. Of critical importance, this study demonstrated that patients with a low ratio of CD8 and CD4 cells to Treg cells ultimately had a lower overall survival, regional recurrence‐free survival, and distant metastasis‐free survival . These findings correlate with previous studies showing that patients with nuclear localization of Treg's and overall high levels of Treg cells in both stroma and cancer nests were associated with increased risk of tumor recurrence and worse disease‐free survival, respectively .…”

Section: Role Of Immune Evasion In Tumor Development and Progressionsupporting

confidence: 87%

“…Malignancy was found to be associated with an increase in the total amount of infiltrating lymphocytes and a transition from T to B cells. Chen et al similarly examined the prognostic implications of the composition of tumor infiltrating lymphocytes based on subtype and found that tongue tumors with higher overall CD4 infiltration and higher ratios of CD4 cells compared to CD3 (pan‐T cells), CD8, and FOXP3 (Treg cells) were associated with absence of lymphovascular invasion, pointing to a potential role for CD4 tumor infiltrating lymphocytes in the prevention of early metastatic disease . Patients with advanced stage tumors also had higher proportions of CD3 cells compared to CD4 or CD8 T cells, suggesting that progression of their disease correlated with a shift toward a more suppressive TME.…”

Section: Role Of Immune Evasion In Tumor Development and Progressionmentioning

confidence: 99%

The promise of immunotherapy in the treatment of young adults with oral tongue cancer

Nasser

John

2020

Laryngoscope Investig Oto

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Historically considered a disease of the older male resulting from cumulative tobacco and alcohol use, more recently we have witnessed a rise in the global incidence of oral tongue squamous cell carcinoma in younger adults, particularly those without any identifiable risk factor exposure. These patients appear to be at higher overall risk for locoregional treatment failure and often experience a more heterogeneous clinical course, with some afflicted with particularly aggressive, rapidly progressive disease.

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Epithelial PD‐L1 expression at tumor front predicts overall survival in a cohort of oral squamous cell carcinomas from Sudan

Gaafar

Osman

Elsheikh

et al. 2022

Clinical & Exp Dental Res

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Background We recently described the tumor immune microenvironment (TIME) in oral squamous cell carcinomas (OSCC) from Sudan by assessing the core of the lesions. However, the invasive tumor front (ITF) is the most active part of OSCC lesions; thus, TIME should also be characterized at the ITF in this patient cohort. Objectives We aimed to evaluate patterns of immune cell infiltration at the ITF in a cohort of OSCC patients from Sudan previously investigated at the tumor center and their association with clinicopathological parameters. Methods This study was performed on a prospective cohort of 22 OSCC patients attending Khartoum Dental Teaching Hospital with a median follow‐up of 48 months. Inflammatory infiltrate densities of CD4‐, CD8‐, FoxP3‐, CD20‐, CD66b‐, M1 (CD80/CD68)‐, M2 (CD163/CD68)‐, and PD‐L1‐positive cells were assessed at the ITF by immunohistochemistry, followed by digital quantitative analysis at the stromal and epithelial compartments separately. Histopathological parameters such as the worst pattern of invasion, differentiation, and tumor budding (TB) were also assessed. Correlations between clinicopathological parameters and survival analysis were investigated using SPSS. Results All inflammatory cell subsets investigated were found to be higher in the stromal compartment as compared to the epithelial one, except for the PD‐L1+ subset. Stromal infiltration with the CD8+ cell subset was associated with low TB. Kaplan–Meier analyses identified higher epithelial and stromal CD4+ cell subsets. The presence of PD‐L1 was found to be associated with unfavorable overall survival. Further, Cox's regression analysis using an age‐ and tumor‐stage‐adjusted model identified epithelial PD‐L1 expression at the ITF as the only independent prognosticator. Conclusions Epithelial PD‐L1 expression at the ITF was found to be an independent prognostic biomarker for OSCC in a cohort of Sudanese patients.

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Prognostic significance of tumor-infiltrating lymphocytes in patients with operable tongue cancer

Cited by 27 publications

References 27 publications

Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma

Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma

The promise of immunotherapy in the treatment of young adults with oral tongue cancer

Epithelial PD‐L1 expression at tumor front predicts overall survival in a cohort of oral squamous cell carcinomas from Sudan

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