Here we chose to dissect the function of immunosuppressive Arg1+ TAM in an immunotherapy-responsive MC38 mouse tumor model during aPD-1 treatment. We used the syngeneic MC38 tumor model given its widespread use in immune-oncology and high macrophage content 10.

The dominant arginine-consuming cells in the TME, displaying a high level of arginase 1 (Arg1, the enzyme for arginine degradation), are dendritic cells (DCs) and tumor associated macrophages (Figures S4B and S4C). MC38 tumor cells expressed fairly low levels of Arg1 even after the uplift on day 11 (Figure 4J). Thus, we decided to artificially ...

2025年2月4日 · Here we found that activation of the lactate receptor HCAR1 signaling pathway induced the expression of chemokines CCL2 and CCL7 in colorectal tumor cells, leading to the recruitment of...

We identified Arg1 + TAM–secreted PF4 as a key determinant of T H 1-T reg cell accumulation in the TME, which suppresses antitumor immunity and promotes tumor growth. Furthermore, PF4 neutralization inhibits T H 1-T reg cell polarization and suppresses tumor growth.

2023年10月12日 · Fbxo38-deficient macrophages reduced the mRNA levels of M2-associated genes (Arg1, Arg2 and Il10) and did not affect the expression of M1-associated genes (Il6 and Il1b) (Fig. 4E).

2021年11月7日 · 以NK细胞为代表的非特异性免疫应答水平持续下降，而树突状细胞在肿瘤内持续累积，并通过激活精氨酸酶 1（Arginase-1，ARG1）和诱导型一氧化氮合成酶（inducible nitric oxide synthetase，iNOS），进一步加深免疫抑制作用。

2024年11月30日 · 作者发现 Arg1 + TAM分泌的 PF4 是 TME 中 TH1-Treg 细胞积累的关键决定因 素 ，它抑制抗肿瘤免疫并促进肿瘤生长。此外，PF4 中和抑制 TH1-Treg 细胞极化并抑制肿瘤生长。

We previously demonstrated that activation of Arg1-specific CD4 + T cells by an Arg1-derived peptide vaccine resulted in tumor growth control and was associated with increased M1/M2 macrophage ratio in the TME of MC38 tumors. 12 In the present study, we investigated whether this antitumor effect was mediated by the direct targeting and ...

The percentage of CD45+ immune cells with Arg1 positivity plotted for MC38 tumors, lung, liver, heart, spleen and (C) tumor-draining lymph node (dLN); collected from 4 mice. Arg1 positivity amongst several MC38 tumor immune c (D) ell populations defined by surface staining

To assess Arg1 cells using conventional and single cell approaches ( Figure 1 A), we used Arg1-eYFP reporter animals that express an iRES-eYFP following endogenous Arg1 [24]. MC38 cancer...

2022年8月9日 · The level of non-specific immune responses represented by NK cells continued to decline, while dendritic cells continued to accumulate in the tumor, and stimulated through the activation of arginase-1 (Arginase-1, ARG1) and inducible nitric oxide synthase (inducible). nitric oxide synthetase, iNOS), further deepening the immunosuppressive effect.

2018年11月12日 · Here we chose to dissect the function of immunosuppressive Arg1+ TAM in an immunotherapy-responsive MC38 mouse tumor model during aPD-1 treatment. We used the syngeneic MC38 tumor model given its widespread use in immune-oncology and high macrophage content [10].

2022年12月6日 · Tbk1-KO MC38 tumors had accelerated tumor growth compared with control tumors (Figure S9 A and Table S3) and were significantly less responsive to anti-PD-1 treatment (Figure 6 B and Table S3). MC38 tumors also grew faster and were more resistant to anti-PD-1 treatment in hIFNAR mice compared with WT mice (Figures 6 C and S9 B and Table S3 ...

2024年11月1日 · Methods C57BL/6 mice harboring MC38 tumor were vaccinated with Arg1 vaccine, and the impact on TAMs in vivo was assessed by multiplex gene expression analysis. Splenic CD4+ T cells from the vaccinated animals were isolated and their impact on macrophages was tested in a co-culture with in vitro M2-differentiated bone marrow-derived macrophages ...

2019年4月1日 · Here, we report that anti–PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment toward a more proinflammatory phenotype. This phenotype was characterized by a decrease in Arginase-I (ARG1) expression and an increase in iNOS, MHCII, and CD40 expression.

2021年11月1日 · We show that ARG1-targeting therapeutic vaccines were able to activate endogenous antitumor immunity in several in vivo syngeneic mouse tumor models and to modulate the cell composition of the tumor microenvironment without causing any associated side effects or systemic toxicity.

在体外，我们根据 wb、pcr、elisa 和流式细胞术等多种技术观察到 gdnp 重编程的 tam 抑制 arg1 释放并最终改善 t 细胞耗竭。 我们还使用体内MC38荷瘤模型并施用GDNP，通过多个指标评估其抗肿瘤效果。

Systemic or myeloid-specific Arg1 deletion improves antigen-induced proliferation of adoptively transferred T-cells and leads to inhibition of tumor growth. Arginase inhibitor was demonstrated to modestly inhibit tumor growth when used alone, and to potentiate antitumor effects of anti-PD-1 monoclonal antibodies and STING agonist.

2021年1月8日 · To confirm the role of reprogramming MDSCs by activated T cells in vivo, we tested the effect of PD-1 mAb on the survival and function of tumor-infiltrating myeloid cells in an ICB-responsive...

Consistently, splenic granulocytes expressed arginase in MC38 tumor-bearing mice, and ruxolitinib nearly ablated arginase 1 (ARG1) protein levels in granulocytes both when administered alone or in conjunction with ICI, suggesting that ruxolitinib modulates not only granulocyte numbers but also expression of suppressive markers (fig. S7G).