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Fig. 2 | Journal of Experimental & Clinical Cancer Research

Fig. 2

From: Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinoma

Fig. 2

Immune superiority and inferiority of T-cells in the TME following nivolumab administration. IL-10 is one of the most important immunoregulatory cytokines that regulate T-cell responses by modulating multiple signaling pathways. Nivolumab induces potent IL-10 secretion in T cells via the activation of the MAPK pathway, in which T cells can activate T cell growth and metabolism, possibly leading to T-cell immune superiority. Based on an in vitro study, nivolumab treatment significantly reduces PD-1 levels in all T-cell populations, suggesting that IL-10 may confer a heterogeneous T-cell response to nivolumab. The engagement of IL-10 with its receptor also activates multiple signaling pathways, particularly the JAK-STAT3 pathway, indicating that nivolumab triggers several biological pathways in the TME. MDSCs exert their immunomodulatory effects via diverse mechanisms, including Arginase-1-mediated depletion of l-arginine and NO production via NOS2. Arginase-1 starves L-arginine in the TME, thus limiting T-cell proliferation. In addition to L-arginine depletion, NO production transforms the TME to promote immune evasion and prolonged NO exposure leads to T-cell apoptosis, causing T-cells to show TME immune inferiority

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