Myeloid checkpoints for cancer immunotherapy

Qian, Yixin; Yang, Ting; Liang, Huan; Deng, Mi

doi:10.21147/j.issn.1000-9604.2022.05.07

Cited by 13 publications

(9 citation statements)

References 148 publications

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“…Simultaneously, B-cell depletion did not promote macrophage polarization into M2 type but increased PDL1 expression on macrophages. This was consistent with other studies on PDL1 expression in myeloid cells promoting the progression of HCC 29 . However, the speci c mechanism by which B cells affect PDL1 expression in macrophages has yet to be thoroughly explored.…”

Section: Discussionsupporting

confidence: 94%

Zinc finger protein 296 promotes hepatocellular carcinoma progression via inducing interaction between macrophages and B cells

Xu,

Wang,

Chen

et al. 2023

Preprint

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Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor survival. Tumor tissues are heterogeneous, with different cell types in the tumor microenvironment, which play different roles in tumorigenesis and tumor progression attached to the prognosis of HCC.This study analyzed HCC RNA-seq for cell-type identification and prognosis by estimating relative subsets of RNA transcript (CIBERSORTx). Analyzing LIHC RNA-seq (n = 423) from TCGA showed that high infiltration of eosinophils promoted HCC progression.Interaction of B cells and macrophages in HCC was detected by the Hepa1-6 orthotopic transplantation mice model and flow cytometer analysis. B cells were correlated with macrophages (r=-0.24) and could affect the expression of PDL1 in macrophages infiltrating in LIHC. Transcription factor Zinc finger protein 296 (ZNF296) might accelerate HCC progression by regulating PAFAH1B3 and H2AFX. HCC patients with high expression of ZNF296 were in the late pathological stage. Moreover, the expression of ZNF296 was positively associated with the abundance of activated B cells (r = 0.185) and macrophages (r = 0.167). Among the survival and dead phenotype related to immune cells identified by SCISSOR analysis, T cells were most correlated to the excellent prognosis of HCC. The normal function of Liver cells and DC cells were also connected with the good prognosis of HCC.This investigation primarily delves into the intricate interplay between the immune microenvironment and the prognosis of HCC, thereby unveiling ZNF296 as a novel diagnostic and therapeutic target for HCC.

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Section: Discussionsupporting

confidence: 94%

Zinc finger protein 296 promotes hepatocellular carcinoma progression via inducing interaction between macrophages and B cells

Xu,

Wang,

Chen

et al. 2023

Preprint

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“…Researches have demonstrated that myeloid checkpoints, receptors located on the surface of myeloid cells, play a role in regulating cell function and activity, enabling tumor immune evasion. 9 Specifically, studies have identified the Siglec family as inhibitory receptors found on innate immune cells. 43 These receptors, on binding to cancer-associated abnormal sialylated glycans, transmit inhibitory signals that facilitate tumor progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, these molecules regulate the immune response against tumors by transmitting inhibitory signals. 9 Among these checkpoints, Siglec-10, an immunoglobulin-like receptor that binds to sialic acid, has gained attention as a crucial player in the immune evasion mechanism employed by tumor cells. 10 Studies have demonstrated that the interaction between the glycoprotein CD24 on the tumor cell surface and Siglec-10 triggers a "don't eat me" signal, impeding the phagocytic activity of TAMs and enabling immune surveillance evasion by tumor cells.…”

Section: How This Study Might Affect Research Practice or Policymentioning

confidence: 99%

Targeting myeloid checkpoint Siglec-10 reactivates antitumor immunity and improves anti-programmed cell death 1 efficacy in gastric cancer

Lv,

Sun,

Fang

et al. 2023

J Immunother Cancer

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ObjectiveImmunotherapy has not yielded satisfactory therapeutic responses in gastric cancer (GC). However, targeting myeloid checkpoints holds promise for expanding the potential of immunotherapy. This study aims to evaluate the critical role of Siglec-10+tumor-associated macrophages (TAMs) in regulating antitumor immunity and to explore the potential of the myeloid checkpoint Siglec-10 as an interventional target.DesignSiglec-10+TAMs were assessed based on immunohistochemistry on tumor microarrays and RNA-sequencing data. Flow cytometry, RNA sequencing, and single-cell RNA-sequencing analysis were employed to characterize the phenotypic and transcriptional features of Siglec-10+TAMs and their impact on CD8+T cell-mediated antitumor immunity. The effectiveness of Siglec-10 blockade, either alone or in combination with anti-programmed cell death 1 (PD-1), was evaluated using an ex vivo GC tumor fragment platform based on fresh tumor tissues.ResultsSiglec-10 was predominantly expressed on TAMs in GC, and associated with tumor progression. In Zhongshan Hospital cohort, Siglec-10+TAMs predicted unfavorable prognosis (n=446, p<0.001) and resistance to adjuvant chemotherapy (n=331, p<0.001), which were further validated in exogenous cohorts. In the Samsung Medical Center cohort, Siglec-10+TAMs demonstrated inferior response to pembrolizumab in GC (n=45, p=0.008). Furthermore, Siglec-10+TAMs exhibited an immunosuppressive phenotype and hindered T cell-mediated antitumor immune response. Finally, blocking Siglec-10 reinvigorated the antitumor immune response and synergistically enhances anti-PD-1 immunotherapy in an ex vivo GC tumor fragment platform.ConclusionsIn GC, the myeloid checkpoint Siglec-10 contributes to the regulation of immunosuppressive property of TAMs and promotes the depletion of CD8+T cells, ultimately facilitating immune evasion. Targeting Siglec-10 represents a potential strategy for immunotherapy in GC.

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“…MDSCs can inhibit both adaptive and innate immunity through a variety of mechanisms, including inhibiting T-cell activation, disabling activated T cells, inhibiting NK cell cytotoxicity, and polarizing macrophages towards tumor progression. High levels of MDSC infiltration in the TME are associated with poor prognosis and treatment resistance of patients [ 57 , 58 ].…”

Section: Altered Tumor Cell Metabolism Influences Immune Cells In The...mentioning

confidence: 99%

The Metabolism and Immune Environment in Diffuse Large B-Cell Lymphoma

Wu,

Meng,

Ran

et al. 2023

Metabolites

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Cells utilize different metabolic processes to maintain their growth and differentiation. Tumor cells have made some metabolic changes to protect themselves from malnutrition. These metabolic alterations affect the tumor microenvironment and macroenvironment. Developing drugs targeting these metabolic alterations could be a good direction. In this review, we briefly introduce metabolic changes/regulations of the tumor macroenvironment and microenvironment and summarize potential drugs targeting the metabolism in diffuse large B-cell lymphoma.

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Myeloid checkpoints for cancer immunotherapy

Cited by 13 publications

References 148 publications

Zinc finger protein 296 promotes hepatocellular carcinoma progression via inducing interaction between macrophages and B cells

Zinc finger protein 296 promotes hepatocellular carcinoma progression via inducing interaction between macrophages and B cells

Targeting myeloid checkpoint Siglec-10 reactivates antitumor immunity and improves anti-programmed cell death 1 efficacy in gastric cancer

The Metabolism and Immune Environment in Diffuse Large B-Cell Lymphoma

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