The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction

Quan, Hongzhi; Shan, Zhongyan; Liu, Ziyi; Liu, Sixuan; Liu, Yang; Fang, Xiaodan; Li, Kun; Wang, Baisheng; Deng, Zhiyuan; Hu, Yanjia; Yao, Zhigang; Huang, Jianyi; Yu, Jianjun; Xia, Kun; Tang, Zhangui; Fang, Liangjuan

doi:10.1007/s00262-020-02479-x

Cited by 38 publications

(37 citation statements)

References 52 publications

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“…One study showed that patients with leukoplakia without malignant transformation had higher numbers of CD3 + cells than patients whose leukoplakia transformed to oral squamous cell carcinoma [46]. Our results agree with existing reports [47][48][49] that presence of a baseline anti-tumor immune cell infiltrate or pre-existing tumor immunity [21] is associated with high levels of tumor infiltrating CD8 + T cells and strongly associated with improved patient survival. Granzyme B + cells were found to be significantly higher in IM and CT of T1-T2 stage tumors compared to T3-T4 tumors suggesting that small tumor size may be attributed to Granzyme B mediated killing of tumor cells [50].…”

Section: Discussionsupporting

confidence: 91%

Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival

et al. 2020

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The tumor immune microenvironment is emerging as a critical player in predicting cancer prognosis and response to therapies. However, the prognostic value of tumor-infiltrating immune cells in Gingivo-Buccal Oral Squamous Cell Carcinoma (GBOSCC) and their association with tumor size or lymph node metastases status require further elucidation. To study the relationship of tumor-infiltrating immune cells with tumor size (T stage) and lymph node metastases (N stages), we analyzed the density of tumor-infiltrating immune cells in archived, whole tumor resections from 94 patients. We characterized these sections by immune-histochemistry using 12 markers and enumerated tumor-infiltrating immune cells at the invasive margins (IM) and centers of tumors (CT). We observed that a higher density of CD3+ cells in the IM and CT was associated with smaller tumor size (T1-T2 stage). Fewer CD3+ cells was associated with larger tumor size (T3-T4 stage). High infiltration of CD3+and CD8+ cells in IM and CT as well as high CD4+ cell infiltrates in the IM was significantly associated with the absence of lymph node metastases. High infiltrates of CD3+ and CD8+ cells in CT was associated with significantly improved survival. Our results illustrate that the densities and spatial distribution of CD3+ and CD8+ cell infiltrates in primary GBOSCC tumors is predictive of disease progression and survival. Based on our findings, we recommend incorporating immune cell quantification in the TNM classification and routine histopathology reporting of GBOSCC. Immune cell quantification in CT and IM may help predict the efficacy of future therapies.

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Section: Discussionsupporting

confidence: 91%

Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival

et al. 2020

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“…Also, the presence of high levels of CD 8+ TILs correlate with longer OS 38 . Among other TILs subpopulations, a high Th17/Treg ratio was found to be associated with better outcomes in OSCC 45 . Taken together, these results suggest that high densities of CD 3+ (pan T cell marker), CD 4+ (T helper cell marker), and CD 8+ (T cytotoxic cell marker) TILs are independent factors for favorable prognosis.…”

Section: Discussionmentioning

confidence: 70%

The immune phenotype of tongue squamous cell carcinoma predicts early relapse and poor prognosis

et al. 2020

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“…The Th17-oriented gene IL17A were also significantly overexpressed in tumors with high peritumoral TLS density. Although the prognostic significance of Th17 infiltration remains controversial in various of malignancies (4,(40)(41)(42). Wang and colleagues revealed IL17A promoted tumor progression via STAT3/NF-kB/Notch1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Peritumoral Tertiary Lymphoid Structures Correlate With Protective Immunity and Improved Prognosis in Patients With Hepatocellular Carcinoma

Liu

et al. 2021

Front. Immunol.

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The existence of intratumoral tertiary lymphoid structure (iTLS) has been reported to correlative with favorable clinical outcomes for patients with hepatocellular carcinoma (HCC). However, little is known about the role of peritumoral TLS (pTLS). This study aimed to investigate the prognostic role of pTLS either alone or jointly with iTLS and the potential association with local immune response in HCC. The formation and cellular composition of TLS was evaluated by hematoxylin & eosin and immunohistochemistry. Evaluation of tumor-infiltrating immune cells and formation of germinal center (GC) inside TLS was performed by immunohistochemistry. The gene expression profiles were analyzed by real-time PCR. In a total of 360 patients from two independent cohorts, the pTLS was identified in most, whereas iTLS could be observed in only approximately 30% of HCC specimens. Patients with high pTLS densities were associated with improved outcomes, those present with characteristic morphology of GC, particularly, showing an even better prognosis. The combination of pTLS and iTLS allowed the identification of patients with best prognosis. Tumors with high pTLS density showed significantly increased expression of Th1-, Th17- and immune suppression-related genes, as well as significantly higher infiltration of CD3+, CD8+ and CD20+ cells and lower infiltration of FOXP3+, CD68+ and PD1+ cells. Conclusively, we provide evidence that pTLS is associated with intratumoral immune infiltration, highlighting the dynamic interplay between pTLS and immune cells recruitment. High pTLS density links to a tumor microenvironment with an active immune reaction and improved patient survival and represents a promising prognostic biomarker for HCC.

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The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction

Cited by 38 publications

References 52 publications

Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival

Density of CD3+ and CD8+ cells in gingivo-buccal oral squamous cell carcinoma is associated with lymph node metastases and survival

The immune phenotype of tongue squamous cell carcinoma predicts early relapse and poor prognosis

Peritumoral Tertiary Lymphoid Structures Correlate With Protective Immunity and Improved Prognosis in Patients With Hepatocellular Carcinoma

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