Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 28, 2024

Tertiary lymphoid structures (TLSs) are defined as aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary (SLOs), the formation of TLSs relies on interaction between tissue inducer (LTi) cells and organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature TLSs, which may lead differences their functions. Growing evidence suggests that associated with various diseases, such cancers, autoimmune transplant rejection, chronic inflammation, infection, even ageing. However, detailed mechanisms behind these clinical associations not yet fully understood. The by TLS maturation localization affect immune function also unclear. Therefore, it necessary enhance understanding development at cellular molecular level, allow us utilize them improve microenvironment. In this review, we delve into composition, mechanism, potential therapeutic applications TLSs. Furthermore, discuss implications role markers response prognosis. Finally, summarize methods for detecting targeting Overall, provide comprehensive aim develop more effective strategies.

Language: Английский

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T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105154 - 105154

Published: May 14, 2024

Language: Английский

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m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling

International Journal of Oral Science, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 10, 2024

Abstract N 1 -methyladenosine (m A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 Pten conditional knockout (2cKO) mice, we found neoplastic transformation oral mucosa was accompanied by increased m A modification levels. Analysis A-associated genes identified TRMT61A as a key writer linked to cancer progression poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m promotes MYC protein synthesis, upregulating programmed death-ligand (PD-L1) expression. Moreover, levels were also elevated tumors treated with oncolytic herpes simplex virus (oHSV), contributing reactive PD-L1 upregulation. Therapeutic inhibition sustained oHSV-induced antitumor immunity reduced tumor growth, representing promising strategy alleviate resistance. These findings indicate that can prevent immune escape after oHSV therapy reducing expression, providing mutually reinforcing combination approach.

Language: Английский

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Single‐Cell RNA‐Sequencing‐Aided Covalent Organic Frameworks‐Based Microneedle Design Targeting Phototherapy Resistant Tumor Cell

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(27)

Published: March 3, 2024

Abstract Covalent organic frameworks (COFs) exhibit immense potential for phototherapy due to their exceptional light absorption, photostability, and biocompatibility. Nevertheless, tumor cells can develop resistance after an initial response, posing a significant challenge complete eradication. In this study, COF‐based photosensitizer, TCN‐PPDA‐COF, is designed with outstanding photothermal properties delivered tumors using microneedles (MN) enhance cancer phototherapy. Single‐cell RNA‐sequencing (scRNA‐seq) technology then utilized explore the mechanisms underlying cell adaptation COF‐mediated The scRNA‐seq analysis revealed that phototherapy‐resistant displayed elevated expression of HIF‐1α VEGF signaling pathways, fostering intratumoral angiogenesis facilitating continued survival during response phenomenon, unique CA‐microneedle patch developed, tailored co‐delivering TCN‐PPDA‐COF inhibitors AL3818 site. CA‐MN patches effectively inhibit in while mediating phototherapy, thereby obliterating cells. 4T1 tumor‐bearing mouse model, achieved nearly regression grafts activated host anti‐tumor immunity, enhancing rate αPD‐1 restraining metastasis recurrence. This study underscored ingenious approach modify COF‐MN through technology.

Language: Английский

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Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216956 - 216956

Published: May 11, 2024

Language: Английский

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Unveiling the role of ACTL6A in uveal melanoma metastasis and immune microenvironment

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113841 - 113841

Published: Jan. 1, 2025

Language: Английский

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Tertiary Lymphoid Structures as a Biomarker in Immunotherapy and Beyond: Advancing Towards Clinical Application

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217491 - 217491

Published: Jan. 1, 2025

Language: Английский

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Identification of a Prognostic Signature Based on Tumor‐Infiltrating B Lymphocyte mRNA in Head and Neck Squamous Cell Carcinoma

Journal of Immunology Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Introduction: Tumor‐infiltrating B cells (TILBs) are an important part of the immune response during tumor regulation. However, significance in immunotherapy has not been fully determined. Methods: In this study, highly expressed genes were obtained by comparing gene expression with that other and named TILB‐mRNAs. Among them, those patients head neck squamous cell carcinoma (HNSCC) identified The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) atlas employed to screen for associated HNSCC prognosis using univariate Cox analysis, least absolute shrinkage selection operator (LASSO) regression a TILB‐related signature was constructed predict patient prognostic risk multivariate analyses. Results: signature, which comprised seven mRNAs ( ZNF439 , KMO KDM5D IFT57 HDAC9 GSAP CCR 7), verified have good ability three independent validation datasets from GEO, predictive affected factors. reflected state infiltration tissue, especially cells, higher scores (RSs) had fewer infiltrating their tumors, cells. also TILBs single‐cell revealing marker differentially different GB subsets. Discussion: This study provides assessment outcome prediction potential targets HNSCC.

Language: Английский

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VISTA blockade alleviates immunosuppression of MDSCs in oral squamous cell carcinoma

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 125, P. 111128 - 111128

Published: Oct. 29, 2023

Language: Английский

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Heterogeneity of tertiary lymphoid structures in cancer

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 4, 2023

The success of immunotherapy approaches, such as immune checkpoint blockade and cellular with genetically modified lymphocytes, has firmly embedded the system in roadmap for combating cancer. Unfortunately, majority cancer patients do not yet benefit from these therapeutic even when prognostic relevance response their tumor entity been demonstrated. Therefore, there is a justified need to explore new strategies inducing anti-tumor immunity. recent connection between formation ectopic lymphoid aggregates at sites patient prognosis, along an effective response, suggests that manipulating occurrence tertiary structures (TLS) may play critical role activating against growing tumor. However, mechanisms governing TLS clear understanding substantial heterogeneity are still lacking. Here, we briefly summarize current state knowledge regarding driving development, outline impact on clinical outcomes patients, discuss appropriate systems modeling help identify protective patients.

Language: Английский

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