Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, other than Abscopal Effect: A Systematic Review

Version 1 : Received: 26 March 2019 / Approved: 28 March 2019 / Online: 28 March 2019 (06:48:37 CET)

A peer-reviewed article of this Preprint also exists.

Longo, V.; Brunetti, O.; Azzariti, A.; Galetta, D.; Nardulli, P.; Leonetti, F.; Silvestris, N. Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review. Cancers 2019, 11, 539. Longo, V.; Brunetti, O.; Azzariti, A.; Galetta, D.; Nardulli, P.; Leonetti, F.; Silvestris, N. Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review. Cancers 2019, 11, 539.

Abstract

Despite the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitor-urinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a high sensibility to immune checkpoint inhibitors, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitors receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.

Keywords

immunocheckpoint inhibitors; chemotherapy; tirosin kinase inhibitors; angiogenesis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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