Miranda Smith
Checkpoints and cure
Immune checkpoints help the immune system to keep itself under control. When they are expressed on immune cells, immune checkpoint markers act as a brake and prevent overly vigorous, and damaging, immune responses. Studies have shown that the repressive effects of immune checkpoints can be reversed. Several antibodies that block immune checkpoints are now in use to treat cancers such as melanoma, lung and bladder cancer. These checkpoint inhibitor drugs can have a really dramatic effect, with some people going into complete and sustained remission after a previously terminal diagnosis. These drugs could possibly be used to treat chronic infections such as HIV, but investigations are still in the exploratory phase. Two of the most studied immune checkpoint markers are PD-1 and CTLA-4. In people living with HIV, both PD-1 and CTLA-4 are increased on immune cells, particularly on those immune cells targeting HIV.
The HIV Persistence in Reservoirs at Alfred, Doherty and the Avenue (PRADA) study was conducted in Melbourne in 2017 and 2018. The study aimed to understand what role the immune checkpoint markers CTLA-4 and PD-1 play in the ongoing presence of HIV in people on antiretroviral treatment. People recruited to the study donated blood cells (by leukapheresis) and also had a lymph node sample taken. The cells from these samples were then studied to see if they have CTLA-4, PD-1, or both on their surface. The different populations of cells were monitored for how much HIV is hiding inside. Professor Sharon Lewin from the Doherty Institute, who headed the study, explains
Immunotherapy has shown tremendous promise in cancer. We are excited about its potential for targeting chronic viral infections like HIV. A clearer understanding of how immune checkpoints contribute to HIV persistence in blood and tissue will be key to determining the role of immune checkpoint inhibitors in HIV treatment.
The PRADA study included sampling of HIV infected cells from both blood and lymph nodes. This is because HIV persistence in immune cells in the blood is known to be quite different from HIV persistence in lymphoid tissue such as lymph nodes. Also, most immune cells are found in the lymphoid tissue. To properly understand the relationship between immune checkpoint markers and HIV, cells from lymphoid tissue really need to be studied. These studies are important because they will help us to understand where HIV remains in the body when someone is on treatment. They also help to identify ways to target residual HIV and boost immune responses against the virus.
.png)