Immune Checkpoint Inhibitors and Infection: What Is the Interplay?

Abstract

Immune checkpoint molecules are receptors expressed on immune cells, especially T-cells, which activate immunosuppressive pathways and lead them to a state known as T-cell exhaustion. Immune checkpoint inhibitors (ICIs) constitute a group of specific antibodies that target these molecules, restoring T-cell effector function. Several ICIs have already been approved by the FDA as therapeutic options for certain malignancies. However, evidence in the literature remains unclear regarding the possible risk of infection in patients receiving this treatment. A thorough examination of existing literature was carried out to investigate whether the use of ICIs increases the likelihood of specific infections and to explore the potential beneficial effects of ICIs on the treatment of infections. Our review found most infectious complications are related to immunosuppressive therapy for immune-related adverse events caused by checkpoint blockade. Current evidence shows that ICIs per se do not seem to generally increase the risk of infection, yet they might increase susceptibility to certain infections, such as tuberculosis. On the other hand, reinvigoration of immune responses triggered by ICIs might play a significant role in pathogen clearance, establishing a possible positive impact of ICIs, especially on chronic infectious diseases, such as HIV infection. Data from preclinical models are limited and larger clinical trials are warranted to shed more light on the effect of immune checkpoint blockade on specific pathogens.

Keywords: Immune checkpoint inhibitors; T-cell exhaustion; complications; immune related adverse effects; infectious diseases; malignancy; opportunistic infections.