External cues to drive B cell function towards immunotherapy

Stoycheva, Diana; Simsek, Hasan; Weber, Willi; Hauser, Anja E.; Klotzsch, Enrico

doi:10.1016/j.actbio.2021.02.026

Cited by 19 publications

(10 citation statements)

References 156 publications

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“…B cells have been shown to function as lymphoid tissue inducer cells, secreting IL-22 to regulate TLS formation [ 40 ]. TLSs, in turn, promote tumour antigen presentation, T cell activation and B cell antibody secretion, thus, triggering the development of adaptive anti-tumour immune responses [ 41 ]. This illustrates the capacity of TLSs to exert effects beyond those on B cells and participate in the activation of the adaptive immune system in a local immune response [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism

Nie

Jia

et al. 2022

Cancers

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Background: Tertiary lymphoid structures (TLSs) are formed by the aggregation of tumour-infiltrating lymphocytes (TILs), which is driven by chemokines or cytokines in the tumour microenvironment. Studies have shown that TLSs are associated with good prognosis in patients with various solid tumours and can improve patient responses to immunotherapy. However, the role of TLSs in hepatocellular carcinoma (HCC) remains controversial, and the underlying molecular mechanism is unclear. Methods: According to haematoxylin-eosin (HE) staining results, HCC patients in Xijing Hospital data and TCGA data were divided into TLS+ and TLS- groups, and Kaplan–Meier (KM) analysis was performed to assess overall survival (OS) and recurrence-free survival (RFS). Immunofluorescence (IF) and immunohistochemistry (IHC) were used to identify TILs in the TLS+ group. Lymphocyte-specific protein tyrosine kinase (LCK), a molecule involved in TLS formation, was explored in LinkedOmics. TILs were divided into two groups by drawing receiver operating characteristic (ROC) curves to calculate cut-off values. Spearman correlation analysis was used to calculate the correlation between LCK and TILs, and the molecular pathways by which LCK regulates immunotherapy were clarified through enrichment analysis. The half-maximal inhibitory concentration (IC50) distribution of sorafenib was observed in groups that varied in LCK expression. Results: According to the HE results, 61 cases in the Xijing Hospital cohort and 195 cases in the TCGA cohort had TLSs, while 89 cases and 136 cases did not. The KM results showed that TLSs had no effect on the OS of HCC patients but significantly affected RFS. The IF/IHC results showed that higher TIL numbers in TLSs were correlated with better prognosis in HCC patients. Spearman correlation analysis showed that LCK expression was positively correlated with TIL numbers. Enrichment analysis showed that upregulation of LCK expression mainly regulated the cytokine signalling pathway, the chemokine signalling pathway and T-cell activation. The IC50 scores of sorafenib in HCC patients with high LCK expression were lower, and the sensitivity was higher. Conclusion: TLSs mainly affected the early RFS of HCC patients but had no effect on OS. The high expression of the TLS formation-related gene LCK can increase the sensitivity of HCC patients to ICIs.

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Section: Discussionmentioning

confidence: 99%

Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism

Nie

Jia

et al. 2022

Cancers

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“…Many researchers have found that the infiltration of immune cells is closely related to the OS or disease-specific survival rate (DSS) of many cancers, including LUAD ( Kadara et al, 2017 ; Hofman, 2020 ; Luo et al, 2020 ). As a kind of immune cells, B cells can fight against tumors through the production of antibodies, antigen royalty or the secretion of immune regulatory factors ( Stoycheva et al, 2021 ). Han et al (2020) found that B cells can be used as an independent indicator of OS prediction in LUAD.…”

Section: Discussionmentioning

confidence: 99%

ALKBH1-8 and FTO: Potential Therapeutic Targets and Prognostic Biomarkers in Lung Adenocarcinoma Pathogenesis

Yan

Cai

et al. 2021

Front. Cell Dev. Biol.

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The AlkB family consists of Fe(II)- and α-ketoglutarate-dependent dioxygenases that can catalyze demethylation on a variety of substrates, such as RNA and DNA, subsequently affecting tumor progression and prognosis. However, their detailed functional roles in lung adenocarcinoma (LUAD) have not been clarified in a comprehensive manner. In this study, several bioinformatics databases, such as ONCOMINE, TIMER, and DiseaseMeth, were used to evaluate the expression profiles and prognostic significance of the AlkB family (ALKBH1-8 and FTO) in LUAD. The expression levels of ALKBH1/2/4/5/7/8 were significantly increased in LUAD tissues, while the expression levels of ALKBH3/6 and FTO were decreased. The main functions of differentially expressed AlkB homologs are related to the hematopoietic system and cell adhesion molecules. We also found that the expression profiles of the AlkB family are highly correlated with infiltrating immune cells (i.e., B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). In addition, DNA methylation analysis indicated that the global methylation levels of ALKBH1/2/4/5/6/8 and FTO were decreased, while the global methylation levels of ALKBH3/7 were increased. In addition, the patients with upregulated ALKBH2 have significantly poor overall survival (OS) and post-progressive survival (PPS). Taken together, our work could provide insightful information about aberrant AlkB family members as potential biomarkers for the diagnostic and prognostic evaluation of LUAD. Especially, ALKBH2 could be served as a therapeutic candidate for treating LUAD.

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“…[20] The main difference between normal and tumor ECM is the increase in deposition of fibrillar matrix components (such as collagen and fibronectin) and an increase in protein crosslinking as well as linearization. In combination, leading to increased stiffness, [21] varying between 100% and 1400% between healthy tissues and their respective solid tumors [21][22][23][24][25][26] (see also Table 1 of our recent review [27] ). As the tumor grows, ECM stiffness increases, and collagen fibers are arranged in a parallel anisotropic orientation (tumor-associated collagen signature), which inhibits non-tumor cells but accelerates tumor cell proliferation.…”

Section: Ecm Microarchitecture and Stiffness Influence Tumor Infiltra...mentioning

confidence: 99%

The solid tumor microenvironment—Breaking the barrier for T cells

Simsek

Klotzsch

2022

BioEssays

Self Cite

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The tumor microenvironment (TME) plays a pivotal role in the behavior and development of solid tumors as well as shaping the immune response against them. As the tumor cells proliferate, the space they occupy and their physical interactions with the surrounding tissue increases. The growing tumor tissue becomes a complex dynamic structure, containing connective tissue, vascular structures, and extracellular matrix (ECM) that facilitates stimulation, oxygenation, and nutrition, necessary for its fast growth. Mechanical cues such as stiffness, solid stress, interstitial fluid pressure (IFP), matrix density, and microarchitecture influence cellular functions and ultimately tumor progression and metastasis. In this fight, our body is equipped with T cells as its spearhead against tumors. However, the altered biochemical and mechanical environment of the tumor niche affects T cell efficacy and leads to their exhaustion. Understanding the mechanobiological properties of the TME and their effects on T cells is key for developing novel adoptive tumor immunotherapies.

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External cues to drive B cell function towards immunotherapy

Cited by 19 publications

References 156 publications

Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism

Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism

ALKBH1-8 and FTO: Potential Therapeutic Targets and Prognostic Biomarkers in Lung Adenocarcinoma Pathogenesis

The solid tumor microenvironment—Breaking the barrier for T cells

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