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Cancers 2019, 11(4), 539; https://doi.org/10.3390/cancers11040539

Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review

1
Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco, 65, 70124 Bari, Italy
2
Medical Oncology Unit, Hospital of Barletta, Viale Ippocrate, 15, 70051 Barletta, Italy
3
Experimental Pharmacology Laboratory, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco, 65, 70124 Bari, Italy
4
Pharmacy Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco, 65, 70124 Bari, Italy
5
Dipartimento di Farmacia-Scienze del Farmaco, University of Bari, Piazza Umberto I, 1, 70121 Bari, Italy
6
Scientific Guidance, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco, 65, 70124 Bari, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work as the first authors.
These authors contributed equally to this work as the last authors.
Received: 26 March 2019 / Revised: 11 April 2019 / Accepted: 12 April 2019 / Published: 15 April 2019
(This article belongs to the Special Issue Immunotherapy, Tumor Microenvironment and Survival Signaling)
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Abstract

Despite that 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 genitourinary 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 such as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a higher expression of immune checkpoint molecules, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors in order 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 the response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitory 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. View Full-Text
Keywords: immune checkpoint inhibitors; chemotherapy; tyrosine kinase inhibitors; angiogenesis immune checkpoint inhibitors; chemotherapy; tyrosine kinase inhibitors; angiogenesis
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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.

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