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A blood test to predict bladder cancer recurrence

In a 100-patient cohort at the Saint-Louis Hospital in Paris, researchers from the CEA and Paris-Diderot University have shown that the rate of certain immune cells in the blood is predictive of bladder cancer recurrence or progression. They suggest using their patented blood test to predict recurrence in other types of cancers.

Published on 18 July 2017
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

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