Tertiary Lymphoid Structures Among the World of Noncanonical Ectopic Lymphoid Organizations

Silva-Sánchez, Aarón; Randall, Troy D.; Meza-Pérez, Selene

doi:10.1007/978-1-4939-8709-2_1

Cited by 5 publications

(10 citation statements)

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“…In autoimmune diseases and allograft rejection, their presence has been associated with an unfavorable clinical evolution (54)(55)(56)(57)(58), as opposed to the favorable outcome observed in cancers associated with their presence. In local infections, their role and prognostic value are more variable and depend on their location, composition and on the considered pathogen (58,59). Remarkably, the study of TLS in these pathological conditions has provided a better understanding of the events that lead to their neogenesis in specific organs and might give some helpful clues in the field of tumor immunology (57).…”

Section: Learning From Tls Study In Non-tumor Inflammatory Diseases To Better Understand Tls Role In Cancermentioning

confidence: 99%

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

et al. 2021

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The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.

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Section: Learning From Tls Study In Non-tumor Inflammatory Diseases To Better Understand Tls Role In Cancermentioning

confidence: 99%

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

et al. 2021

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“…However, like pDCs, fDCs may be present in inflammatory conditions and chronic infections of non‐lymphoid tissues 13,33 . Our study only found CD21 in two intraoral mucosa (IM) samples, and the control was entirely negative.…”

Section: Discussionmentioning

confidence: 50%

“…12 However, like pDCs, fDCs may be present in inflammatory conditions and chronic infections of non-lymphoid tissues. 13,33 Our study only found CD21 in two intraoral mucosa (IM) samples, and the control was entirely negative. In some other specimens, intense LP-clustered CD21 immunoexpression was observed, probably corresponding to ectopic lymphoid follicles.…”

Section: Conflict Of Interest Statementmentioning

confidence: 66%

“…transient component, whose function is to decrease inflammation and infection. 33 No papers using CD21 in oral mucosal LE have been found so far and there is only one in cutaneous LE, against which our comparison was performed. B al anescu et al analyzed histological aspects and the expression of several markers, including CD21 of 10 SLE cutaneous lesions and 10 healthy controls and found little CD21 expression in the dermis compared to normal controls.…”

Section: Discussionmentioning

confidence: 99%

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Oral lupus erythematosus: Immunohistochemical evaluation of CD1a, CD21, CD123, and langerin expression in dendritic cells

Marques,

Hsieh,

Lourenço

et al. 2024

J Cutan Pathol

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BackgroundDendritic cells participate in the pathophysiology of lupus erythematosus (LE), which are studied in systemic and cutaneous forms; however, little is known about their oral manifestations.MethodsThe expressions of dendritic cell markers (including CD1a, CD21, CD123, and langerin) were investigated by immunohistochemistry technique. Sixty intraoral and lower lip LE lesions, and additional 10 control samples were collected from 2003 to 2019. They were topographically analyzed in the epithelium (EP), lamina propria (LP), epithelial junction (JUN), and deep perivascular (PV) areas.ResultsThe expression of CD1a was decreased in the EP (p = 0.003) and increased in the deep PV area (p = 0.002). Langerin immunostaining showed no significant decrease in EP (p = 0.944); however, it increased in LP (p = 0.012) and JUN (p = 0.006). CD21 was expressed in only two specimens (EP, p = 0.012; LP, p < 0.001; deep PV area, p = 0.018). CD123 expression increased in all topographies (EP, p < 0.005; LP, p < 0.001, JUN, p < 0.001; deep PV, p < 0.001). The comparison between vermilion and intraoral mucosa LE lesions suggested that sun‐exposed sites showed higher expression of CD123 (EP, p = 0.024; LP, p = 0.047; JUN, p = 0.001).ConclusionsCD1a, langerin, and CD123 expressions were detected coincidently surrounding the inflammatory infiltrate in oral LE, suggesting that these cells may play an important role in immune response. Interestingly, plasmacytoid dendritic cells showed increased CD123 expression in sun‐exposed site lesions, which point out a possible function in their pathogenesis. Further studies are needed to confirm this hypothesis.

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“…A previous study showed that lymphocytes in TLOs overproduce the proinflammatory cytokines under a sustained situation caused an unsolvable inflammation status in the kidney ( 24 ). Additionally, TLOs do not have capsular-like lymph nodes ( 25 ). Thus, the cells and cytokines of TLOs can expand to the renal interstitial part and occupy broad areas of parenchyma in the kidneys, which enforced the inflammation of the kidneys ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study

Wang

Cheng

et al. 2022

Front. Med.

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BackgroundTertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet.MethodsConsecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid–Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan–Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria.ResultsA total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p < 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria.ConclusionIn this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.

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Tertiary Lymphoid Structures Among the World of Noncanonical Ectopic Lymphoid Organizations

Cited by 5 publications

References 129 publications

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Oral lupus erythematosus: Immunohistochemical evaluation of CD1a, CD21, CD123, and langerin expression in dendritic cells

Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study

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