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Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer

1
Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, IL 60612, USA
2
Jesse Brown VA Medical Center, Chicago, IL 60612, USA
3
Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL 60612, USA
4
University of Illinois Hospital & Health Sciences System Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(1), 9; https://doi.org/10.3390/ph13010009
Received: 23 December 2019 / Revised: 2 January 2020 / Accepted: 4 January 2020 / Published: 7 January 2020
(This article belongs to the Collection Protein Kinases and Cancer)
Mitogen-activated protein kinase (MAPK) signaling networks serve to regulate a wide range of physiologic and cancer-associated cell processes. For instance, a variety of oncogenic mutations often lead to hyperactivation of MAPK signaling, thereby enhancing tumor cell proliferation and disease progression. As such, several components of the MAPK signaling network have been proposed as viable targets for cancer therapy. However, the contributions of MAPK signaling extend well beyond the tumor cells, and several MAPK effectors have been identified as key mediators of the tumor microenvironment (TME), particularly with respect to the local immune infiltrate. In fact, a blockade of various MAPK signals has been suggested to fundamentally alter the interaction between tumor cells and T lymphocytes and have been suggested a potential adjuvant to immune checkpoint inhibition in the clinic. Therefore, in this review article, we discuss the various mechanisms through which MAPK family members contribute to T-cell biology, as well as circumstances in which MAPK inhibition may potentiate or limit cancer immunotherapy. View Full-Text
Keywords: cancer; mitogen-activated protein kinase; T cells; Programmed cell death protein 1; Programmed death-ligand 1; cytotoxic T-lymphocyte-associated protein 4; T-cell anergy; immunotherapy cancer; mitogen-activated protein kinase; T cells; Programmed cell death protein 1; Programmed death-ligand 1; cytotoxic T-lymphocyte-associated protein 4; T-cell anergy; immunotherapy
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Kumar, S.; Principe, D.R.; Singh, S.K.; Viswakarma, N.; Sondarva, G.; Rana, B.; Rana, A. Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer. Pharmaceuticals 2020, 13, 9.

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