Single-cell RNA sequencing unveils the communications between malignant T and myeloid cells contributing to tumor growth and immunosuppression in cutaneous T-cell lymphoma

Du, Yuxin; Cai, Yun; Lv, Yan; Zhang, Lishen; Yang, Hao; Liu, Quanzhong; Hong, Minghui; Teng, Yue; Tang, Weiyan; Ma, Rong; Wu, Jianqiu; Wu, Jinjin; Wang, Qianghu; Chen, Hongshan; Li, Kening; Feng, Jifeng

doi:10.1016/j.canlet.2022.215972

Cited by 30 publications

(12 citation statements)

References 54 publications

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“…In lymph node metastasized tumors, LAMP3+ DCs showed a stronger interaction with Tregs to enhance immunosuppression (32). In pancreatic adenocarcinoma, urothelial bladder carcinoma, and cutaneous T-cell lymphoma, LAMP3+ DCs also promote immune tolerance and immunosuppression through interacting with CD8 +T or tumor-infiltrating Tregs (33)(34)(35). LAMP3+ DCs highly expressed CD80 and CD86, through interaction of CD80-CD28, CD80-CTLA4, CD86-CD28, and CD86-CTLA4, which might modulate CXCL13+/CD4+, and FOXP3+/CD4+ Tregs activities (36,37).…”

Section: Discussionmentioning

confidence: 99%

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Wang

Jin

et al. 2023

Front. Immunol.

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BackgroundThe disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.MethodsWe retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3high and LAMP3low expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.ResultsCompared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.ConclusionsLAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response.

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Section: Discussionmentioning

confidence: 99%

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Wang

Jin

et al. 2023

Front. Immunol.

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“…Further to that, it has been discovered that CCL13 protein expression is augmented in the plasma of pediatric Hodgkin’s lymphoma patients and is related to a sluggish early response; and for Hodgkin’s lymphoma patients, biologically-based risk stratification algorithms that incorporate CCL13 could be taken into consideration to enhance treatment results and reduce toxicity ( 126 , 127 ). In cutaneous T-cell lymphoma (CTCL), CCL13 + monocytes/macrophages play a role in mediating immunosuppression by interacting with malignant T cells, and blocking the S100A9-TLR4 interaction with tasquinimod has been shown to inactivate the NF-κB pathway, leading to inhibition of CTCL tumor cell growth and induction of apoptosis ( 22 ).…”

Section: Ccl13 and Cancermentioning

confidence: 99%

CCL13 and human diseases

Dai

Wang

et al. 2023

Front. Immunol.

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CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it’s fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.

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“…A recent single-cell study by Du et al additionally reported the enrichment of T/NK and myeloid cells as a common feature in the skin ecosystem of advanced-stage CTCL patients [ 52 ]. More specifically, enhanced crosstalk between malignant CTCL populations and CCL13+ mono/macrophages as well as LAMP3+ conventional DCs (cDCs) were strongly identified across advanced-stage patients.…”

Section: The Tumor Microenvironment (Tme) and Immune Response In Ctclmentioning

confidence: 99%

“…More specifically, enhanced crosstalk between malignant CTCL populations and CCL13+ mono/macrophages as well as LAMP3+ conventional DCs (cDCs) were strongly identified across advanced-stage patients. By disentangling intercellular communications in the CTCL skin microenvironment, the inhibitory interactions of CD47-SIRPA, MIF-CD74, and CCR1-CCL18 interactions were found to take place between malignant T cells and mono/macrophages [ 52 ]. Additionally, a potent interaction between the most highly expressed gene in the malignant T cell compartment, that of S100A9, and toll-like receptor 4 (TLR4) notably enriched in the CCL13+ mono/macrophage population was detected across CTCL samples, with this axis previously reported to have a tumor-promoting and immunosuppressive role in other cancer types [ 53 , 54 ].…”

Section: The Tumor Microenvironment (Tme) and Immune Response In Ctclmentioning

confidence: 99%

Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma

Kalliara

Belfrage

Gullberg

et al. 2023

Cancers

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Mycosis fungoides (MF) and Sézary syndrome (SS) are two closely related clinical variants of cutaneous T-cell lymphomas (CTCL). Previously demonstrated large patient-to-patient and intra-patient disease heterogeneity underpins the importance of personalized medicine in CTCL. Advanced stages of CTCL are characterized by dismal prognosis, and the early identification of patients who will progress remains a clinical unmet need. While the exact molecular events underlying disease progression are poorly resolved, the tumor microenvironment (TME) has emerged as an important driver. In particular, the Th1-to-Th2 shift in the immune response is now commonly identified across advanced-stage CTCL patients. Herein, we summarize the role of the TME in CTCL evolution and the latest studies in deciphering inter- and intra-patient heterogeneity. We introduce spatially resolved omics as a promising technology to advance immune-oncology efforts in CTCL. We propose the combined implementation of spatially guided and single-cell omics technologies in paired skin and blood samples. Such an approach will mediate in-depth profiling of phenotypic and molecular changes in reactive immune subpopulations and malignant T cells preceding the Th1-to-Th2 shift and reveal mechanisms underlying disease progression from skin-limited to systemic disease that collectively will lead to the discovery of novel biomarkers to improve patient prognostication and the design of personalized treatment strategies.

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Single-cell RNA sequencing unveils the communications between malignant T and myeloid cells contributing to tumor growth and immunosuppression in cutaneous T-cell lymphoma

Cited by 30 publications

References 54 publications

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

CCL13 and human diseases

Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma

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