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Cancers (Basel). 2019 Jul 23;11(7). pii: E1037. doi: 10.3390/cancers11071037.

AP-1 Transcription Factors as Regulators of Immune Responses in Cancer.

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Department of Oncology, Ludwig Institute for Cancer Research-Lausanne Branch, University of Lausanne, Épalinges, 1066 Lausanne, Switzerland.
Department of Pathology, Children's Hospital of Wisconsin & Medical College of Wisconsin, Medical College of Winsconsin, Milwaukee, WI 53226, USA.
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Department of Pathology and Cytology, Karolinska University Hospital, 17176 Stockholm, Sweden.
Department of Systems Biology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030, USA.


Immune check point blockade therapy has revolutionized the standard of cancer treatment and is credited with producing remarkable tumor remissions and increase in overall survival. This unprecedented clinical success however is feasible for a limited number of cancer patients due to resistance occurring before or during a course of immunotherapy, which is often associated with activation of oncogenic signaling pathways, co-inhibitory checkpoints upregulation or expansion of immunosuppressive regulatory T-cells (Tregs) in the tumor microenviroment (TME). Targeted therapy aiming to inactivate a signaling pathway such as the Mitogen Activated Protein Kinases (MAPKs) has recently received a lot of attention due to emerging data from preclinical studies indicating synergy with immune checkpoint blockade therapy. The dimeric transcription factor complex Activator Protein-1 (AP-1) is a group of proteins involved in a wide array of cell processes and a critical regulator of nuclear gene expression during T-cell activation. It is also one of the downstream targets of the MAPK signaling cascade. In this review, we will attempt to unravel the roles of AP-1 in the regulation of anti-tumor immune responses, with a focus on the regulation of immune checkpoints and Tregs, seeking to extract useful insights for more efficacious immunotherapy.


AP-1; CTLA-4; PD-1; PD-L1; Tregs; immune checkpoints; immunotherapy; targeted therapy; transcription factors

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