Deciphering Repertoire of B16 Melanoma Reactive TCRs by Immunization, In Vitro Restimulation and Sequencing of IFNγ-Secreting T Cells

Izosimova, Anna V.; Yuzhakova, Diana V.; Skatova, Valeria D; Volchkova, Lilia N; Загайнова, Е. В.; Chudakov, Dmitriy M.; Шаронов, Г. В.

doi:10.3390/ijms22189859

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…In our experiment, we used an unmodified B16F0 cell line for melanoma induction. This tumor model is almost non-immunogenic and the anti-PD1 therapy produces stable antitumor immunity only in 30% of mice [13]. Similar findings were also observed in patients with melanoma [14].…”

Section: Tumor Weightsupporting

confidence: 78%

Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy

Tibenský¹,

Blasko²,

Vargovič³

et al. 2023

neo

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Experimental and clinical data have shown that the nervous system can significantly stimulate the initiation and progression of melanoma. In support of this, approaches that reduce the transmission of signals from peripheral nerves to effector tissues reduce the recurrence of melanoma. Therefore, we investigated the effect of topical application of the local anesthetic Pliaglis (7% lidocaine and 7% tetracaine) on the growth of melanoma induced by intradermal application of B16F0 cells in mice without treatment and in mice treated with the anti-PD-1 antibody. We found that application of Pliaglis to melanoma significantly reduced its growth and this effect was even pronounced in mice treated with the anti-PD-1 antibody. To determine the mechanisms and pathways responsible for the observed effect, the in vitro effect of incubating melanoma cells with lidocaine and/or tetracaine and the in vivo gene expression of cancer and immune-related factors, percentage of immune cells, gene expression of selected neurotransmitter receptors and nerve growth factors in melanoma tissue were studied. We found that lidocaine and tetracaine significantly reduced the viability of B16F0 cells in vitro. In mice with melanoma, Pliaglis potentiated the effect of anti-PD-1 antibody on gene expression of COX-2, IL-1β, IL-6, CCL11, F4/80, CD206, and NCR1. In addition, Pliaglis increased the gene expression of α9nACHR and 5-HT2a receptors and decreased the gene expression of nerve growth factor receptor (p75NTR) and p53. We also observed Pliaglis-mediated changes in myeloid populations. Topical application of this local anesthetic cream decreased the CD11b + Gr1population and increased the CD11b + Gr1 high population. Our data suggest that Pliaglis reduces melanoma growth through a direct effect on melanoma cells as well as through modulation of the immune response. The involvement of nervous system-related signaling in the inhibitory effect of Pliaglis on melanoma is inconclusive from our data.

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Section: Tumor Weightsupporting

confidence: 78%

Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy

Tibenský¹,

Blasko²,

Vargovič³

et al. 2023

neo

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“…Experiments were performed on freshly excised LNs on 10–11th and 14–15th days after tumor implantation. The time points and, respectively, tumor sizes were selected based on our previous studies on B16F0 melanoma model and immune check-point inhibitors [ 23 , 24 , 25 ]. The LNs from intact mice without tumors served as a control.…”

Section: Introductionmentioning

confidence: 99%

FLIM of NAD(P)H in Lymphatic Nodes Resolves T-Cell Immune Response to the Tumor

Izosimova

Shirmanova

Shcheslavskiy

et al. 2022

IJMS

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Assessment of T-cell response to the tumor is important for diagnosis of the disease and monitoring of therapeutic efficacy. For this, new non-destructive label-free methods are required. Fluorescence lifetime imaging (FLIM) of metabolic coenzymes is a promising innovative technology for the assessment of the functional status of cells. The purpose of this work was to test whether FLIM can resolve metabolic alterations that accompany T-cell reactivation to the tumors. The study was carried out on C57Bl/6 FoxP3-EGFP mice bearing B16F0 melanoma. Autofluorescence of the immune cells in fresh lymphatic nodes (LNs) was investigated. It was found that fluorescence lifetime parameters of nicotinamide adenine dinucleotide (phosphate) NAD(P)H are sensitive to tumor development. Effector T-cells in the LNs displayed higher contribution of free NADH, the form associated with glycolysis, in all tumors and the presence of protein-bound NADPH, associated with biosynthetic processes, in the tumors of large size. Flow cytometry showed that the changes in the NADH fraction of the effector T-cells correlated with their activation, while changes in NADPH correlated with cell proliferation. In conclusion, FLIM of NAD(P)H in fresh lymphoid tissue is a powerful tool for assessing the immune response to tumor development.

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Deciphering Repertoire of B16 Melanoma Reactive TCRs by Immunization, In Vitro Restimulation and Sequencing of IFNγ-Secreting T Cells

Cited by 2 publications

References 46 publications

Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy

Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy

FLIM of NAD(P)H in Lymphatic Nodes Resolves T-Cell Immune Response to the Tumor

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