Multiregion single‐cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer

Wang, Wei; Zhong, Yu; Zhuang, Zhenkun; Xie, Junping; Lu, Yueer; Huang, Chengzhi; Sun, Yan; Wu, Liang; Yin, Jianhua; Yu, Hang; Jiang, Zhiqiang; Wang, Shanshan; Wang, Chunqing; Zhang, Yuanhang; Huang, Yilin; Han, Chongyin; Zhong, Zhenggang; Hu, Jialin; Ouyang, Ying; Liu, Huisheng; Yu, Mengya; Wei, Xiaochan; Chen, Dandan; Huang, Lizhen; Hou, Yong; Lin, Zhanglin; Liu, Shiping; Ling, Fei; Yao, Xueqing

doi:10.1002/ctm2.253

Cited by 65 publications

(60 citation statements)

References 68 publications

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“…In the Apc Min/+ CRC mouse model, an expansion of IgA + lymphocytes in the tumor microenvironment was identified [200]. This matches the dominancy of plasma cells in advanced tumors for CRC patients, where the B cell subpopulation IgA + IGLC2 + was associated with poor prognosis [201]. Noteworthy is the observation that pre-B like cells may have antitumor functions in the early stages of CRC development [201], but perhaps this becomes less effective when they differentiate into plasma cells in advanced CRC.…”

Section: Iga-microbiota In Colorectal Cancersupporting

confidence: 54%

Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis

et al. 2021

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Mucosal surfaces in the gastrointestinal tract are continually exposed to native, commensal antigens and susceptible to foreign, infectious antigens. Immunoglobulin A (IgA) provides dual humoral responses that create a symbiotic environment for the resident gut microbiota and prevent the invasion of enteric pathogens. This review features recent immunological and microbial studies that elucidate the underlying IgA and microbiota-dependent mechanisms for mutualism at physiological conditions. IgA derailment and concurrent microbiota instability in pathological diseases are also discussed in detail. Highlights of this review underscore that the source of IgA and its structural form can dictate microbiota reactivity to sustain a diverse niche where both host and bacteria benefit. Other important studies emphasize IgA insufficiency can result in the bloom of opportunistic pathogens that encroach the intestinal epithelia and disseminate into circulation. The continual growth of knowledge in these subjects can lead to the development of therapeutics targeting IgA and/or the microbiota to treat life threatening diseases.

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Section: Iga-microbiota In Colorectal Cancersupporting

confidence: 54%

Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis

et al. 2021

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“…The significance of the tumor microenvironment has been investigated in this study. Cross-talk between immune cells and tumor cells modulated tumor metastasis and therapy response [ 13 ]. Our cell-to-cell communication analysis revealed the existence of tumor-immune escape in lymph nodes and unraveled the respective ligand-receptor pairs.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

et al. 2021

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Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including CD44 + / ALDH2 + /ALDH6A1 + breast cancer stem cells (BCSCs), which had a copy-number variants profile similar to that of normal breast tissue. Importantly, BCSCs existed only in primary tumors and evolved into metastatic clusters infiltrating into lymph nodes. Furthermore, transcriptome data suggested that NECTIN2-TIGIT-mediated interactions between metastatic breast cancer cells and tumor microenvironment (TME) cells, which promoted immune escape and lymph node metastasis. This study is the first to delineate the transcriptome profile of breast cancer lymph node metastasis using single-cell RNA sequencing. Our findings offer novel insights into the mechanisms underlying breast cancer metastasis and have implications in developing novel therapies to inhibit the initiation of breast cancer metastasis.

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“…More detailed information is discussed in our previous study. 36 After dismounting, raw reads were cleaned using Cutadapt (version 1.15) and mapped to hg38 using STAR (version 020201). Gene expression levels of each cell were quantified using RSEM (version 1.3.0) and combined in R (version 3.6.2).…”

Section: Methodsmentioning

confidence: 99%

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

Liu

Zhong

et al. 2021

Molecular Therapy - Oncolytics

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Increasing evidence indicates that mature B cells in the adjacent tumor tissue, both as an intermediate state, are vital in advanced colorectal cancer (CRC), which is associated with a low survival rate. Developing predictive biomarkers that detect the tipping point of mature B cells before lymph node metastasis in CRC is critical to prevent irreversible deterioration. We analyzed B cells in the adjacent tissues of CRC samples from different stages using the dynamic network biomarker (DNB) method. Single-cell profiling of 725 CRC-derived B cells revealed the emergence of a mature B cell subtype. Using the DNB method, we identified stage II as a critical period before lymph node metastasis and that reversed difference genes triggered by DNBs were enriched in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway involving B cell immune capability. DHX9 (DEAH-box helicase 9) was a specific para-cancerous tissue DNB key gene. The dynamic expression levels of DHX9 and its proximate network genes involved in B cell-related pathways were reversed at the network level from stage I to III. In summary, DHX9 in mature B cells of CRC-adjacent tissues may serve as a predictable biomarker and a potential immune target in CRC progression.

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Multiregion single‐cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer

Abstract: Integrated single-cell RNA sequencing technologies reveal a high-resolution immune landscape of colorectal primary tumors and liver metastasis, identifying major immune cell types and distinct cell functional states of T and B cells as well as predictions of complex cell-cell interactions.

Cited by 65 publications

References 68 publications

Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis

Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis

Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

Single-cell transcriptomics reveal DHX9 in mature B cell as a dynamic network biomarker before lymph node metastasis in CRC

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