HLA-G, a shield against the immune system
Human leukocyte antigen G (HLA-G) is a molecule involved in immune tolerance. Normally, it is expressed only in the setting of pregnancy, on the surface of placental cells, where the molecule plays a role in protecting the fetus from attack by the maternal immune system. However, HLA-G expression is also detected in several other settings, such as organ transplants or neoplasms.
In a study performed in 2002 and in partnership with Prof. Alain Carpentier of the Broussais Hospital, Edgardo D. Carosella and his CEA team at the Saint-Louis Hospital (a part of AP-HP, the greater Paris public hospital system) showed that the expression of HLA-G in heart transplants significantly diminished acute rejection and eliminated chronic rejection. However, the expression of HLA-G in tumors is correlated with poor prognosis, showing a sort of "other side of the coin". Indeed, if a tumor is not detected by the immune system, this latter can do nothing to destroy it. HLA-G expression by cancer cells thus affords them protection from the host's immune system and resultantly the opportunity to develop or recur.
In cancer, the expression of HLA-G is associated with disease course and this latter with recurrence and spread. The molecule, even with tumors, acts as a shield to inhibit immune response.
The rate of CD8+ cells also expressing ILT2 is predictive of bladder cancer recurrence and progression
With the objectives of anticipating disease course and reducing recurrence risk, Professors Edgardo D. Carosella[1] and François Desgrandchamps[2] analyzed HLA-G expression in bladder cancer cells to better understand how the immune system's response against these cells could be shut down, leaving them to multiply with near impunity. Their work confers a real clinical advance as it addresses a frequent cancer notable for a significant immunological component but nonetheless lacking effective treatments.
Peripheral CD8+ cells, also called cytotoxic T cells, are responsible for the destruction of cancer cells. They may also express another receptor, called ILT2, that appears to modulate CD8+ activation. A study performed on blood samples taken over three years from more than 100 patients with bladder cancer at the Saint-Louis Hospital showed that tumor recurrence was associated with the percentage of circulating CD8+ cells expressing ILT2.
Patients who experienced recurrence had a rate of circulating CD8+ ILT2+ cells greater than 40%, signifying a weakened, and thus more-easily inhibited, immune system as concerns the cancer. Therefore, the rate of circulating CD8+ cells expressing ILT2 can identify patients at greater risk of recurrence. Through biostatistical analyses on patient cohorts, the researchers determined that rates <20% and >40% indicated respectively low and high risks of recurrence.
The AP-HP, Paris Diderot University and the CEA filed a patent application to enable the development of an evaluation kit. The resulting technology, developed at the AP-HP's Saint-Louis Hospital, won the 2017 APinnov "Promising Patent" Trophy. The kit developed by Professors Carosella and Desgrandchamps should benefit from testing at a larger scale and in other cancers. Involving only a simple blood sample and a classic, widely-available flow cytometry technique, the test brings a simple and non-invasive solution to most hospitals and private laboratories.
This result has been shared through a press release.
To identify and count the CD8+ ILT2+ lymphocytes, the blood test developed by the AP-HP's Saint-Louis Hospital uses flow cytometry, a technology commonly available in hospitals. © D. Morel / CEA