Fig. 5: MAO-A blockade for cancer immunotherapy—syngeneic mouse tumor model studies. | Nature Communications

Fig. 5: MAO-A blockade for cancer immunotherapy—syngeneic mouse tumor model studies.

From: Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy

Fig. 5: MAO-A blockade for cancer immunotherapy—syngeneic mouse tumor model studies.

a–e Studying the effect of MAOI treatment on IL-4/IL-13-induced BMDM polarization in vitro (n = 4). a Experimental design. Wild-type BMDMs were stimulated with IL-4/IL-13 with or without MAOI treatment. MAOIs (monoamine oxidase inhibitors) studied were phenelzine (Phe; 20 μM), clorgyline (Clo; 20 μM), moclobemide (Moc; 200 μM), and pirlindole (Pir; 20 μM). NT no MAOI treatment. b FACS analyses of ROS levels in BMDMs. c FACS analyses of CD206 expression on BMDMs. d, e QPCR analyses of Chi3l3 (d) and Arg1 (e) mRNA expression in BMDMs. ***p < 0.001. f–j Studying the TAM-related cancer immunotherapy potential of MAOI treatment in a B16-OVA melanoma syngeneic mouse tumor model. f Experimental design. B6 wild-type mice were treated with clodronate liposomes (Clod) to serve as TAM-depleted experimental mice or treated with vehicle liposomes (Veh) to serve as TAM-intact control mice. Phe phenelzine treatment, NT no phenelzine treatment. g Tumor growth. h Tumor volume at day 18 (***p < 0.001). i FACS analyses of CD206 expression on TAMs of TAM-intact experimental mice (*p = 0.0164). j FACS analyses of intracellular Granzyme B production in tumor-infiltrating CD8+ T cells of all experimental mice (NT, *p = 0.0257; Veh, **p = 0.0025). Veh NT, n = 7; Veh Phe, n = 8; Clod NT, n = 7; Clod Phe, n = 7. k–o Studying the cancer therapy potential of MAOI treatment in combination with anti-PD-1 treatment in the B16-OVA melanoma and MC38 colon cancer syngeneic mouse tumor models (n = 5). k Experimental design. Tumor-bearing mice were treated with anti-PD-1 antibody (aPD-1) or isotype control (Iso), together with or without phenelzine (Phe) treatment. NT no Phe treatment. l B16-OVA tumor growth. m B16-OVA tumor volume at day 18. n MC38 tumor growth. o MC38 tumor volume at day 27. *p < 0.05, **p < 0.01 and ***p < 0.001. Representative of three experiments. Analysed by one-way ANOVA (b–e, h, j, m, o) or by Student’s t test (i). Statistics are all two-sided. Source data are provided as a Source Data file.

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