Cancer immunotherapy strategies involve manipulating patients’ immune system to augment tumor immunity and represent a paradigm shift in the treatment cancer . Main immunotherapeutic strategies include regimes such as cytokines, vaccines, an oncolytic virus, adoptive cell therapy, and immune checkpoint blockade. The approach that has sparked the most interest involves inhibition or activation of specific immune checkpoints to regulate T cell function in order to boost patients’ own ability to fight cancer. Under normal physiological conditions, the immune checkpoints are crucial for maintaining self-tolerance to prevent autoimmunity and also to protect tissues from damage during infections. However, in cancer, the function of immune checkpoints is dysregulated in order to suppress the ongoing T cell-mediated antitumor immune responses. Numerous inhibitory (e.g., CTLA-4, PD-1, TIGIT, LAG3, IDO) as well as stimulatory (e.g., OX40, 4-1BB, CD27, STING) immune signaling pathways are being currently targeted for cancer immunotherapy. Two of them, CTLA-4 and PD-1, have been most actively studied in the clinic up till now, and numerous positive clinical trials led to approval of therapies targeting these two pathways across several tumor types. However, despite these significant advances, the majority of patients do not respond favorably to cancer immunotherapies. This may be due to additional mechanisms that can influence the enhancement of T cell function at play, in addition to multiple mechanisms used by tumors to evade the immune system. Hence, future effective immunotherapies will likely involve novel combinations of different immunotherapeutic approaches in addition to targeted therapies that are personalized for maximal benefit.
Immune signaling Immune checkpoints Co-stimulation Cytotoxic T cells Immunotherapy
This is a preview of subscription content, log in to check access.
Nishimura H, Minato N, Nakano T, Honjo T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998;10(10):1563–72.CrossRefPubMedGoogle Scholar
Ledford H. (2017). Next-generation cancer drugs boost immunotherapy responses. Early clinical trial data suggest that combining medicines improves treatment. Nat News. https://doi.org/10.1038/nature.2017.22092.