Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Yamaguchi, Hana; Hiroi, Miki; Mori, Kensaku; Ushio, Ryosuke; Matsumoto, Ari; Yamamoto, Nobuharu; Shimada, Jun; Ohmori, Yoshihiro

doi:10.3390/cancers13081835

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…It was reported that MDSCs were capable of inducing Treg, 34 which might result in a positive feedback loop that augmented immunosuppression. These findings were consistent with a recent study 35 . In addition, we found that the expression of CTLA‐4 on T cells and the proportion of Treg increased significantly after anti‐PD‐1 therapy, which may offset the effect of therapy.…”

Section: Discussionsupporting

confidence: 93%

“…These findings were consistent with a recent study. 35 In addition, we found that the expression of CTLA‐4 on T cells and the proportion of Treg increased significantly after anti‐PD‐1 therapy, which may offset the effect of therapy. These results suggested that PD‐1 blockade combined with CTLA‐4 blockade and Treg clearance may display a better therapeutic effect.…”

Section: Discussionmentioning

confidence: 77%

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Dynamic changes of exhaustion features in T cells during oral carcinogenesis

et al. 2022

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Objectives This study aimed to clarify the dynamic changes of exhaustion features in T cells during oral carcinogenesis. Materials and Methods Mice were randomly divided into 4NQO group and control group. The exhaustion features of CD4 + and CD8 + T cells of both groups were detected by flow cytometry. Furthermore, multiplex immunohistochemistry was used to evaluate the expression of inhibitory receptors in human normal, dysplastic, and carcinogenesis tissues. Finally, anti‐PD‐1 antibody treatment was performed at the early premalignant phase of oral carcinogenesis. Results The proportion of naive T cells in 4NQO group was lower than those in control group, while the proportion of effector memory T cells was higher in 4NQO group. The expression of inhibitory receptors on CD4 + and CD8 + T cells increased gradually during carcinogenesis. In contrast, the secretion of cytokines by CD4 + and CD8 + T cells decreased gradually with the progression stage. Strikingly, those changes occurred before the onset of oral carcinogenesis. The expression of inhibitory receptors on T cells increased gradually as the human tissues progressed from normal, dysplasia to carcinoma. Interestingly, PD‐1 blockade at the early premalignant phase could reverse carcinogenesis progression by restoring T cell function. Conclusions T‐cell dysfunction was established at the early premalignant phase of oral carcinogenesis; PD‐1 blockade at the early premalignant phase can effectively reverse T‐cell exhaustion features and then prevent carcinogenesis progression.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 77%

Dynamic changes of exhaustion features in T cells during oral carcinogenesis

et al. 2022

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“…Tumor-infiltrating lymphocytes are an important prognostic factor for cancer progression and a key player in cancer immunotherapy. CCL2, CCL17 and CCL22 are cytokines with a role in T-cell recruitment [ 59 , 60 ]. Despite the role of CCL2 in recruiting both cytotoxic T cells (CTL) and monocytes to tumor sites [ 61 , 62 ], studies have shown that enhancement of the CCL2/CCR2 axis [ 63 ] or inhibition of CCL2 nitration [ 64 ] in antitumor therapy significantly promotes T-cell infiltration and exerts antitumor effects.…”

Section: Discussionmentioning

confidence: 99%

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

Wang

Zhang

et al. 2023

IJMS

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Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.

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“…21,22,35 In addition to the cell types mentioned above, other immune cell types are also relevant for different diseases. 36–41…”

Section: Discussionmentioning

confidence: 99%

Rapid qPCR-based quantitative immune cell phenotyping in mouse tissues

Huang,

Demmler,

Mohamed Abdou

et al. 2023

Journal of Investigative Medicine

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The immune microenvironment plays an important role in the regulation of diseases. The characterization of the cellular composition of immune cell infiltrates in diseases and respective models is a major task in pathogenesis research and diagnostics. The assessment of immune cell populations in tissues by either flow cytometry (FACS) or immunohistochemistry (IHC) are the two most common techniques presently applied for this purpose but are cost intensive, laborious, and sometimes also limited by the availability of suitable antibodies. Complementary rapid qPCR-based approaches exist for the human situation but are lacking for experimental mouse models. Accordingly, we developed a robust, rapid RT-qPCR-based approach to determine and quantify the abundance of prominent immune cell populations such as T cells, helper T (Th) cells, cytotoxic T cells, Th1 cells, B cells, and macrophages in mouse tissues. The results were independently validated by the gold standards IHC and FACS in corresponding tissues and showed high concordance.

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Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Cited by 8 publications

References 34 publications

Dynamic changes of exhaustion features in T cells during oral carcinogenesis

Dynamic changes of exhaustion features in T cells during oral carcinogenesis

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

Rapid qPCR-based quantitative immune cell phenotyping in mouse tissues

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