Next Article in Journal
The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease
Next Article in Special Issue
Staphylococcal Bicomponent Pore-Forming Toxins: Targets for Prophylaxis and Immunotherapy
Previous Article in Journal
Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure
Previous Article in Special Issue
Monoclonal Antibody Therapy and Renal Transplantation: Focus on Adverse Effects
Toxins 2014, 6(3), 914-933; doi:10.3390/toxins6030914

Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander”

Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy
* Author to whom correspondence should be addressed.
Received: 27 November 2013 / Revised: 21 January 2014 / Accepted: 18 February 2014 / Published: 3 March 2014
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
View Full-Text   |   Download PDF [3904 KB, uploaded 3 March 2014]   |   Browse Figure


Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific “immune-related adverse events” (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique “innocent bystander” effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment.
Keywords: checkpoint-blocking antibodies; immune response; toxicity; immune therapies; ipilimumab checkpoint-blocking antibodies; immune response; toxicity; immune therapies; ipilimumab
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Gelao, L.; Criscitiello, C.; Esposito, A.; Goldhirsch, A.; Curigliano, G. Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander”. Toxins 2014, 6, 914-933.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert