Macrophage CD5L is a target for cancer immunotherapy

Sanchez‐Moral, Lidia; Paul, Tony; Martori, Clara; Font-Díaz, Joan; Sanjurjo, Lucía; Aran, Gemma; Téllez, Érica; Blanco, Julià; Carrillo, Jorge; Ito, Masaoki; Tuttolomondo, Martina; Ditzel, Henrik J.; Fumagalli, Caterina; Tapia, Gustavo; Sidorova, Julia; Masnou, Helena; Fernández-Sanmartín, Marco-Antonio; Lozano, Juanjo; Vilaplana, Cristina; Rodriguez-Cortés, Alhelí; Armengol, Carolina; Valledor, Annabel F.; Kremer, Leonor; Sarrias, Maria-Rosa

doi:10.1016/j.ebiom.2023.104555

Cited by 11 publications

(4 citation statements)

References 57 publications

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“… 51 In a study of lung adenocarcinoma, the immunosuppressive phenotype of macrophages was blocked in vitro by an anti-CD5L monoclonal antibody. 52 In our study, CD5L expression was significantly reduced in HCC tissues and correlated with the expression of TBX21 and EOMES, suggesting that CD5L may be involved in regulating Tex. Alongside complement proteins such as C5b, C6, C8, and C9, C7 forms part of the membrane attack complex (MAC).…”

Section: Discussionsupporting

confidence: 57%

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC

Li,

Zhou,

et al. 2023

IJGM

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Purpose Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated. Patients and Methods We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the “CellChat” R package. Results Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results. Conclusion TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.

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Section: Discussionsupporting

confidence: 57%

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC

Li,

Zhou,

et al. 2023

IJGM

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“…In general, the key to cancer metastasis is migration and invasion, and the TME plays an important role in these processes. For example, TAMs with high CD5L expression have been shown to be associated with poor prognosis in patients with papillary lung adenocarcinoma [45], and subtypes of high-grade serous ovarian cancer macrophages have been revealed to be associated with the prognosis of tumor extracellular matrix signatures [46]. Moreover, analysis of the TME in metastatic breast cancer identified several tumor-promoting genes in bone marrow cells and confirmed diversity in CAFs, endothelial cells, and mural cells [47].…”

Section: Discussionmentioning

confidence: 95%

TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

SONG,

KIM,

CHOI

et al. 2024

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Lung cancer has the highest mortality rate among all cancers, in part because it readily metastasizes. The tumor microenvironment, comprising blood vessels, fibroblasts, immune cells, and macrophages [including tumor-associated macrophages (TAMs)], is closely related to cancer cell growth, migration, and invasion. TAMs secrete several cytokines, including interleukin (IL)-1β, which participate in cancer migration and invasion. p21-activated kinase 1 (PAK1), an important signaling molecule, induces cell migration and invasion in several carcinomas. Tonicityresponsive enhancer-binding protein (TonEBP) is also known to participate in cancer cell growth, migration, and invasion. However, the mechanisms by which it increases lung cancer migration remain unclear. Therefore, in this study, we aimed to elucidate the mechanisms by which IL-1β and TonEBP affect lung cancer cell migration and invasion. We found that A549 cocultured-MΦ-secreted IL-1β induced A549 cell migration and invasion via the PAK1 pathway. TonEBP deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1βinduced migration and invasion. PAK1 phosphorylation, which was promoted by IL-1β, was reduced when TonEBP was depleted. These results suggest that TonEBP plays an important role in IL-1β induction and invasiveness of A549 cells via the PAK1 pathway. These findings could be valuable in identifying potential targets for lung cancer treatment. Abbreviations NSCLCNon-small cell lung cancer TAMs Tumor-associated macrophages TME Tumor microenvironment MΦ Macrophage IL-1βInterleaukine-1 beta TonEBP Tonicity-responsive enhancer-binding protein PAK1 p21-activated kinase 1 JNK c-Jun N-terminal kinase NF-κB Nuclear factor kappa B

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“…Macrophages are implicated in many cancers, including mesothelioma and lung cancer [56,84,[125][126][127][128] , where they can make up to half of the total tumour burden [125,[129][130][131] . Indeed, tumour-associated macrophage (TAM) numbers are often associated with poorer outcome [132][133][134] due to their ability to promote tumour growth [59,125,135] , invasion, metastasis [132,136] , neoangiogenesis [51,59,71] and therapeutic resistance [137][138][139] .…”

Section: Tumour-associated Macrophagesmentioning

confidence: 99%