Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

Zhou, Zhaokai; Dang, Qin; Xu, Hui; Lv, Jinxiang; Li, Huanyun; Han, Xinwei

doi:10.7150/thno.76854

Cited by 65 publications

(32 citation statements)

References 198 publications

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“…Several studies have endeavored to integrate chemokines and CAR-T cells to fight cancer, with ongoing investigations focused on CXCR2-modified CAR-T cells that have been shown to induce complete tumour regression and immunological memory in aggressive tumors [ 130 ].…”

Section: Roles Of Cytokines In Drug Resistance In Multiple Myelomamentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs’ survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called “osteoblastic and vascular niches”, thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs–BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs’ proliferation and survival, PCs–BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.

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Section: Roles Of Cytokines In Drug Resistance In Multiple Myelomamentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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“…In recent years, tumor immunotherapy has become a hot spot in the eld of tumor treatment research and is also considered one of the most promising treatment methods. Immunotherapy has achieved great success in the treatment of many tumors [37]; however, its therapeutic effect in PC is minimal [38]. In this study, we analyzed the correlation between MINDY2 in PC and immunity and found that MINDY2 was signi cantly and positively correlated with in ltration scores of B cells, T cells CD8+, neutrophil, macrophage, and myeloid dendritic cells in PC, and although there was no statistical signi cance between MINDY2 and T cells CD4+, it can be concluded that the expression level of CD4 + T cells was greater in the MINDY2 high expression group than in the low expression group.…”

Section: Discussionmentioning

confidence: 99%

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway

Liu

Zhu

et al. 2022

Preprint

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The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the role of MINDY2, a member of the motif interacting with Ub-containing novel DUB family (MINDY), as a newly identified deubiquitinating enzyme, in PC is still unclear. In this study, we found that MINDY2 expression is elevated in PC tissue (clinical samples) and was associated with poor prognosis. We also found that MINDY2 is associated with pro-carcinogenic factors such as epithelial-mesenchymal transition (EMT), inflammatory response, and angiogenesis; the ROC curve suggested that MINDY2 has a high diagnostic value in PC. Immunological correlation analysis suggested that MINDY2 is deeply involved in immune cell infiltration in PC and is associated with immune checkpoint-related genes. In vivo and in vitro experiments further suggested that elevated MINDY2 promotes PC proliferation, invasive metastasis, and EMT. Meanwhile, actinin alpha 4 (ACTN4) was identified as a MINDY2-interacting protein by mass spectrometry and other experiments, and ACTN4 protein levels were significantly correlated with MINDY2 expression. The ubiquitination assay confirmed that MINDY2 stabilizes the ACTN4 protein level by deubiquitination. The pro-oncogenic effect of MINDY2 was significantly inhibited by silencing ACTN4. Bioinformatics Analysis and Western blot experiments further confirmed that MINDY2 stabilizes ACTN4 through deubiquitination and thus activates the PI3K/AKT/mTOR signaling pathway. In conclusion, we identified the oncogenic role and mechanism of MINDY2 in PC, suggesting that MINDY2 is a viable candidate gene for PC and may be a therapeutic target and critical prognostic indicator.

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“…Tumour cells escape being destroyed by the immune system because the immune cells, such as neutrophils, monocytes, macrophages, dendritic cells, natural killer cells, and B and T lymphocytes, are suppressed [138]. Besides, the tumour immune responses are barred from immune checkpoint activations, thereby causing immune evasion [139]. Therefore, the immune evasion is eliminated by suppressing and inhibiting the both mechanisms.…”

Section: Immune Evasion Therapiesmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

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Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

Cited by 65 publications

References 198 publications

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

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