Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers

Xu, Yu; Zhuang, Wei; Feng, Mei; Zhu, Dongqing; Mei, Shenglin; Wu, Zhongen; Feng, Qingyang; Chang, Wenju; Ji, Meiling; Liu, Chenglong; Zhu, Yuanyuan; Shen, Lian; Yang, Fan; Chen, Yijiao; Feng, Yuxiong; Xu, Jiacheng; Zhu, Di

doi:10.1016/j.celrep.2022.111295

Cited by 39 publications

(32 citation statements)

References 34 publications

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“…In addition, CD19 is closely associated with colorectal cancers as a marker of B cells. [ 24 ] Therefore, distinguishing from the B cell types obtained from cluster 3 annotation, we labeled cluster 7 as CD19+CD20+B, as indicated in Figure 12b.…”

Section: Resultsmentioning

confidence: 99%

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Reliable Identification and Interpretation of Single‐Cell Molecular Heterogeneity and Transcriptional Regulation using Dynamic Ensemble Pruning

Fan

Wang

et al. 2023

Advanced Science

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Unsupervised clustering is an essential step in identifying cell types from single-cell RNA sequencing (scRNA-seq) data. However, a common issue with unsupervised clustering models is that the optimization direction of the objective function and the final generated clustering labels in the absence of supervised information may be inconsistent or even arbitrary. To address this challenge, a dynamic ensemble pruning framework (DEPF) is proposed to identify and interpret single-cell molecular heterogeneity. In particular, a silhouette coefficient-based indicator is developed to determine the optimization direction of the bi-objective function. In addition, a hierarchical autoencoder is employed to project the high-dimensional data onto multiple low-dimensional latent space sets, and then a clustering ensemble is produced in the latent space by the basic clustering algorithm. Following that, a bi-objective fruit fly optimization algorithm is designed to prune dynamically the low-quality basic clustering in the ensemble. Multiple experiments are conducted on 28 real scRNA-seq datasets and one large real scRNA-seq dataset from diverse platforms and species to validate the effectiveness of the DEPF. In addition, biological interpretability and transcriptional and post-transcriptional regulatory are conducted to explore biological patterns from the cell types identified, which could provide novel insights into characterizing the mechanisms.

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Section: Resultsmentioning

confidence: 99%

“…H(T) + H(P) (24) where I(• ) denotes the Mutual Information between the inputs, H(• ) was the entropy of the partitioning and NMI(• ) ∈ [0, 1]. NMI(• ) = 0 means that there was no correlation between prediction and truth.…”

Section: Nmi(t P) = I(t P) √mentioning

confidence: 99%

Reliable Identification and Interpretation of Single‐Cell Molecular Heterogeneity and Transcriptional Regulation using Dynamic Ensemble Pruning

Fan

Wang

et al. 2023

Advanced Science

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“…6 7 Several studies have shown a critical role of the immune microenvironment in the progression of CRCLM. [8][9][10] Therefore, it is necessary to investigate the characterization of immune contexture to evaluate its effect on the prognosis of CRCLM patients (CRCLMs).…”

Section: What This Study Addsmentioning

confidence: 99%

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Zhang

Wang

Zuo

et al. 2023

J Immunother Cancer

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BackgroundTertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).Methods603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.ResultsT score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.ConclusionsThe distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

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“…The role of B cells in cancer progression is much less understood than that of T cells. Growing evidence suggested that tumor-infiltrating B cells may exert both tumor suppressive and tumor promoting effects ( Gu et al, 2019 ; Xu et al, 2022 ). During exercise, circulating B-cell counts increased mildly immediately and in proportion to exercise duration and intensity ( Ronsen et al, 2001 ).…”

Section: Physical Activity-dependent Modulation Of Immune Cellsmentioning

confidence: 99%

Physical activity prevents tumor metastasis through modulation of immune function

Zheng

Zhang²,

Yang³

et al. 2022

Front. Pharmacol.

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Metastasis is responsible for 90% of deaths in cancer patients. Most patients diagnosed with metastatic cancer will die within 5 years. PA is good for health and has become an emerging adjuvant therapy for cancer survivors. Regular moderate exercise substantially lowers the incidence and recurrence of several cancers, alleviates cancer-related adverse events, enhances the efficacy of anti-cancer treatments, and improves the quality of life of cancer patients. Revealing the mechanisms of PA inhibiting tumor metastasis could upgrade our understanding of cancer biology and help researchers explore new therapeutic strategies to improve survival in cancer patients. However, it remains poorly understood how physical activity prevents metastasis by modulating tumor behavior. The immune system is involved in each step of tumor metastasis. From invasion to colonization, immune cells interact with tumor cells to secret cytokines and proteases to remodel the tumor microenvironment. Substantial studies demonstrated the ability of physical activity to induce antitumor effects of immune cells. This provides the possibility that physical activity can modulate immune cells behavior to attenuate tumor metastasis. The purpose of this review is to discuss and summarize the critical link between immune function and exercise in metastasis prevention.

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Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers

Cited by 39 publications

References 34 publications

Reliable Identification and Interpretation of Single‐Cell Molecular Heterogeneity and Transcriptional Regulation using Dynamic Ensemble Pruning

Reliable Identification and Interpretation of Single‐Cell Molecular Heterogeneity and Transcriptional Regulation using Dynamic Ensemble Pruning

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases

Physical activity prevents tumor metastasis through modulation of immune function

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