Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma

Li, Qunxing; Liu, Xiangqi; Wang, Dikan; Wang, Yanqiong; Lu, Huanzi; Wen, Sheng; Fang, Juan; Cheng, Bin; Wang, Zhi

doi:10.1038/s41368-020-00092-3

Cited by 89 publications

(81 citation statements)

References 47 publications

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“…CD8 + T cells have been shown to induce lipid peroxidation in cancer cells and sensitize cells to ferroptosis via IFNγ [ 40 ]. A higher density of these immune cells was found in tertiary lymphoid structure-positive patients and contributed to a better 5-year overall survival for OSCC [ 41 ]. Th2 cells and Tregs play a notable role in tumour immune evasion.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Zhang

Chen

et al. 2021

BMC Cancer

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Background The prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients. Methods The mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups. Results A prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator’s contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status. Conclusion This study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Zhang

Chen

et al. 2021

BMC Cancer

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“…They found that the presence of TLS was associated with increased 5 years overall-and relapse-free survival, and importantly, both immature and mature TLS conveyed equally positive outcomes. 58 In contrast, Posch et al (2018) delineated that TLS in colorectal tumors exhibited different degrees of maturation which were associated with differential prognostic values. 47 In particular, mature TLS containing germinal centers had a more positive prognostic outcome compared with immature TLS.…”

Section: Do Immature and Mature Tls Differentially Impact A Patient'smentioning

confidence: 99%

“…In addition, other gene signatures containing 8 and 19 genes related to the presence of T follicular helper cells, type 1 helper CD4 + T cells and B cells were reported in breast 54 and gastric 55 cancers. Collectively, this has led to the detection of TLS in lung, 41 , 45 , 56 , 57 oral squamous cell carcinoma, 58 breast, 54 , 59–61 colon, 51 , 62 stomach, 55 , 63 , 64 liver, 65 sarcoma, 3 , 66 , 67 bladder, 68 clear cell renal cell carcinoma, 4 ovarian cancer 46 , 69 and melanoma 4 , 5 , 15 , 44 , 50 , 70 ( Table 1 ). TLS formation and densities vary between tumor types, and between patients.…”

Section: Tertiary Lymphoid Structures In Cancer – Prognostic and Predmentioning

confidence: 99%

“… 57 Oralsquamous cell carcinoma Tongue, bucca, gingiva and other locations Primary tumors Naive Tumor H&E staining – TLS and germinal centers – CD3 + T cells, B cells (CD20 + ), mature DC (DC-Lamp + ) and PNAd + HEV like vessels Favorable N.A. 58 Breast ER − HER2 − ; HER2 + ; ER + HER2 + Primary tumors 2 cohorts – one treated with neoadjuvant chemotherapy Tumor Tfh cell signature and CXCL13 gene expression Favorable Associated with a higher rate of pathological complete response 54 Breast HER2 + Primary tumors Chemotherpay and trastuzumab Peri-tumoral tissue H&E staining – TLS in adjacent tissue and germinal centers N.D. No impact of TLS. Increased disease free-survival with moderate to abundant tumor infiltrating lymphocytes 59 Breast ER, PR and HER2 ± Primary tumors Naive Tumor and peri-tumoral tissue CD3 + CD4 + and CD8 + T cells, B cells (CD20 + ), FDC (CD21 + ) – germinal centers (Bcl6 + ), PNAd + HEV like vessels Associated with aggressive tumors N.A.…”

Section: Tertiary Lymphoid Structures In Cancer – Prognostic and Predmentioning

confidence: 99%

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Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

et al. 2021

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Tertiary lymphoid structures (TLS) are ectopic cellular aggregates that resemble secondary lymphoid organs in their composition and structural organization. In contrast to secondary lymphoid organs, TLS are not imprinted during embryogenesis but are formed in non-lymphoid tissues in response to local inflammation. TLS structures exhibiting a variable degree of maturation are found in solid tumors. They are composed of various immune cell types including dendritic cells and antigen-specific B and T lymphocytes, that together, actively drive the immune response against tumor development and progression. This review highlights the successive steps leading to tumor TLS formation and its association with clinical outcomes. We discuss the role played by tumor-infiltrating B lymphocytes and plasma cells, their prognostic value in solid tumors and immunotherapeutic responses and their potential for future targeting.

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“…A large number of studies demonstrated that the tumor microenvironment is closely related to the prognosis and effectiveness of immunotherapy [45][46][47]. TLS is a crucial component of tumor immune microenvironment [5,48], which not only facilitating the recruitment of immune cells or play an anti-tumor role, but also act as a predictor for the prognosis of various cancer [4,7,10,15,22,24,34,39]. However, several studies reported the effect of TLS expression on prognosis and clinicopathological characteristics of solid tumor patient remains controversial [9,11,13,15].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

Zhao¹,

Ding²,

Zhou³

et al. 2021

Int. J. Med. Sci.

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Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors. Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors. Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 -0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 -0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 -0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer. Conclusion:High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.

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Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma

Cited by 89 publications

References 47 publications

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors

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