Poly-ICLC, a multi-functional immune modulator for treating cancer.

Abstract

Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies. In this review, we discuss the potential of poly-ICLC as a multi-functional immune modulator for treating cancer and its impact on the 3 above mentioned barriers. We describe the unique capacity of poly-ICLC in stimulating 2 separate pattern recognition receptors, TLR3 and cytosolic MDA5 and the consequences of these activations on cytokines and chemokines production. We emphasize the role of poly-ICLC as an adjuvant in the setting of peptide-based cancer vaccines and in situ tumor vaccination by mimicking natural immune responses to infections. Finally, we summarize the impact of poly-ICLC in enhancing T infiltration into the tumor parenchyma and address the implication of this finding in the clinic.

• Authors: Hussein Sultan, Andres M Salazar, Esteban Celis
• Journal: Seminars in immunology (Semin Immunol) Vol. 49 Pg. 101414 (06 2020) ISSN: 1096-3618 [Electronic] England
• PMID: 33011064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cytokines
• Immunologic Factors
• Receptors, Pattern Recognition
• Toll-Like Receptor 3
• Polylysine
• poly ICLC
• IFIH1 protein, human
• Interferon-Induced Helicase, IFIH1
• Carboxymethylcellulose Sodium
• Poly I-C

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carboxymethylcellulose Sodium (analogs & derivatives, pharmacology, therapeutic use)
• Cytokines (metabolism)
• Humans
• Immunity, Innate (drug effects)
• Immunologic Factors (pharmacology, therapeutic use)
• Immunomodulation (drug effects)
• Interferon-Induced Helicase, IFIH1 (metabolism)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Neoplasms (drug therapy, etiology, metabolism, pathology)
• Poly I-C (immunology, pharmacology, therapeutic use)
• Polylysine (analogs & derivatives, immunology, pharmacology, therapeutic use)
• Receptors, Pattern Recognition (metabolism)
• Toll-Like Receptor 3 (metabolism)