Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system

Yago Pico de Coaña; Aniruddha Choudhury; Rolf Kiessling

doi:10.1016/j.molmed.2015.05.005

Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system

Trends Mol Med. 2015 Aug;21(8):482-91. doi: 10.1016/j.molmed.2015.05.005. Epub 2015 Jun 16.

Authors

Yago Pico de Coaña¹, Aniruddha Choudhury², Rolf Kiessling³

Affiliations

¹ Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden. Electronic address: yagopico@gmail.com.
² Medical Department, Bristol-Myers Squibb, Mulgrave, Australia.
³ Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.

PMID: 26091825
DOI: 10.1016/j.molmed.2015.05.005

Abstract

Immune checkpoint receptors are crucial molecules for fine-tuning immune responses. Checkpoint signaling dampens T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. It is well established that tumors use several mechanisms to avoid elimination by the immune system, and one involves hijacking these checkpoint pathways. Checkpoint blockade therapy utilizes monoclonal antibodies to release the brakes from suppressed T cells, allowing them to be activated and recover their antitumor activity. This therapeutic approach has revolutionized cancer immunotherapy, and extraordinary increases in overall survival were noted, first with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) and subsequently with anti-PD-1 (programmed cell death receptor-1) in melanoma and other malignancies.

Keywords: CTLA-4; MDSCs; PD-1; cancer immunotherapy; checkpoint blockade.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
CTLA-4 Antigen / antagonists & inhibitors
CTLA-4 Antigen / immunology
CTLA-4 Antigen / metabolism
Cancer Vaccines
Combined Modality Therapy
Humans
Immunosuppression Therapy
Immunosuppressive Agents / pharmacology
Immunosuppressive Agents / therapeutic use
Immunotherapy
Ligands
Molecular Targeted Therapy
Myeloid Cells / immunology
Myeloid Cells / metabolism
Neoplasms / genetics
Neoplasms / immunology*
Neoplasms / metabolism
Neoplasms / therapy*
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / metabolism
Radiotherapy
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Treatment Outcome

Substances

Antineoplastic Agents
CTLA-4 Antigen
Cancer Vaccines
Immunosuppressive Agents
Ligands
Programmed Cell Death 1 Receptor