The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study

Fukuhara, Mitsuro; Muto, Satoshi; Inomata, Sho; Yamaguchi, H.; Mine, Hayato; Takagi, Hironori; Ozaki, Yuki; Watanabe, Masayuki; Inoue, Takuya; Yamaura, Takumi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, T.; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Suzuki, Hiroyuki

doi:10.1007/s00262-021-03067-3

Cited by 20 publications

(10 citation statements)

References 40 publications

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“…Although there are several studies that demonstrated TILs or TLSs were correlated with the preoperative NLR, 31,37 there was no relationship between TILs or TLSs and NLR in this study. However, even in the studies that showed the correlation between TILs or TLSs and NLR, they did not suggest the reasonable mechanism, warranting further study.…”

Section: Discussioncontrasting

confidence: 79%

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma

Matsuda,

Yamamoto,

Habu

et al. 2023

Ann Surg Oncol

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Background The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissue has been related to the prognosis in various malignancies. Meanwhile, neutrophil-to-lymphocyte ratio (NLR) as a systemic inflammation marker also has been associated with the prognosis in them. However, few reports have investigated the relationship between pulmonary metastases from sarcoma and these biomarkers. Methods We retrospectively recruited 102 patients undergoing metastasectomy for pulmonary metastases from uterine leiomyosarcoma at Okayama University Hospital from January 2006 to December 2019. TILs and TLSs were evaluated by immunohistochemical staining of surgically resected specimens of pulmonary metastases using anti-CD3/CD8/CD103/Foxp3/CD20 antibodies. NLR was calculated from the blood examination immediately before the most recent pulmonary metastasectomy. We elucidated the relationship between the prognosis and these factors. Because we considered that the status of tumor tissue and systemic inflammation were equally valuable, we also assessed the impact of the combination of TILs or TLSs and NLR on the prognosis. Results As for TILs, CD3-positive cells and CD8-positive cells were correlated with the prognosis. The prognosis was significantly better in patients with CD3-high group, CD8-high group, TLSs-high group, and NLR-low group, respectively. The prognosis of CD8-high/NLR-low group and TLSs-high/NLR-low group was significantly better than that of CD8-low/NLR-high group and TLSs-low/NLR-high group, respectively. Conclusions CD3-positive TILs, CD8-positive TILs, TLSs, and NLR are correlated with the prognosis, respectively. The combination of CD8-positive TILs or TLSs and NLR may be the indicators to predict the prognosis of patients with pulmonary metastases from uterine leiomyosarcoma.

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Section: Discussioncontrasting

confidence: 79%

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma

Matsuda,

Yamamoto,

Habu

et al. 2023

Ann Surg Oncol

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“…Related to the cellular component of TLS, a readily evaluable biomarker is represented by the percentage of peripheral blood lymphocytes and the existence of TLSs. Literature data describes the impact of this parameter or the neutrophil/lymphocyte ratio in peripheral blood on the postoperative prognosis of oncological patients, such as patients with squamous cell lung tumors [ 28 ] or urothelial carcinomas, where an increased number of TLSs associated with a reduced neutrophil/lymphocyte ratio has been reported to increase the response to pembrolizumab therapy [ 29 ]. In our study, the presence of an increased number of TLSs was significantly correlated with an increased number of peripheral lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of Cervical Cancer-Associated Tertiary Lymphoid Structures (TLSs) and Their Specific Interrelation With Clinicopathological Parameters

Balan,

Cimpean,

Secosan

et al. 2024

Cureus

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Objective: The study investigates morphological variants of tertiary lymphoid structures (TLSs) in relation to cervical cancer development, from intraepithelial neoplastic lesions to invasive carcinomas with locoregional lymph node metastases. Materials and methods: This retrospective analysis comprised 100 cervical cancer cases who had had total hysterectomy with lymphadenectomy in the Obstetrics and Gynecology Clinic of the Municipal Emergency Clinical Hospital of Timisoara, Romania, from 2020 to 2023. Bilateral ilio obturator lymphadenectomy and total hysterectomy were used to acquire biopsy samples. The presence of germinal centers, other stromal structures, TLS density, topography relative to the tumor lesion, and malignant cell islets are used to evaluate and classify TLS. Results: We first globally evaluated the total number of TLSs (TLS.T). We observed topographically two places in the cervical stroma: TLS immediately peritumorally positioned and TLS away from tumor lesions. Invasive carcinomas have bigger superficial TLSs with a well-defined germinal center. As they approached the tumor, TLSs increased in size and density. We also detected a special type of TLS associated with nerve fibers, which we named tertiary lymphoid structures associated with nerves (TLS.N). The total number of TLSs did not correlate with age, but 85.71% of patients presenting TLS.N were aged between 59 and 72 years old. Our findings showed a strong correlation between age (postmenopausal, p = 0.005) and TLS-N presence. Similarly, TLS parameters evolved with tumor differentiation. Only in the TLS.N group did the tumoral grading (G) 3 correlate with TLS (p = 0.041), while TLS.T did not correlate with G. All TLS.N. patients, except one, had lymphovascular invasion and massive histiocytosis. On the first point, TLS.N correlated with lymphovascular invasion (p = 0.032). Conclusion: Tertiary lymphoid structures associated with nerves have not been previously reported in cervical cancer, and their effects on prognosis and aggression are unknown. There was a substantial association between TLSs.N presence and age over 60, suggesting it is exclusive to menopausal women. They were also substantially connected with lymphovascular invasion and G3, suggesting they may be a poor cervical cancer prognostic factor.

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“…In non-small cell lung cancer (NSCLC), high density of peritumoral TLS and intratumoral TLS are associated with early stage and better postoperative survival. 99,100 Tregs is commonly seen as the immunosuppressive component in TIME, 98 Devi-Marulkar et al 101 reported that the Tregs in NSCLC-associated TLS inhibits the proliferation and cytokine secretion of CD4+ T cells, which causes poor clinical outcome. However, antibodies against CTLA4 and glucocorticoid-induced TNF receptor-related protein lift this inhibition, which suggests that Treg function is the key point of antitumor immunity in NSCLC-related TLS.…”

Section: Tls-related Immune Responses In Lung Cancermentioning

confidence: 99%

“…In non‐small cell lung cancer (NSCLC), high density of peritumoral TLS and intratumoral TLS are associated with early stage and better postoperative survival 99,100 . Tregs is commonly seen as the immunosuppressive component in TIME, 98 Devi‐Marulkar et al 101 .…”

Section: Role Of Tls In Cancermentioning

confidence: 99%

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

Wang,

et al. 2024

MedComm

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Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in‐depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.

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The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study

Cited by 20 publications

References 40 publications

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma

Prognostic Impact of Tumor-Infiltrating Lymphocytes, Tertiary Lymphoid Structures, and Neutrophil-to-Lymphocyte Ratio in Pulmonary Metastases from Uterine Leiomyosarcoma

Heterogeneity of Cervical Cancer-Associated Tertiary Lymphoid Structures (TLSs) and Their Specific Interrelation With Clinicopathological Parameters

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

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