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A Blood Test to Predict Bladder Cancer Recurrence

In a cohort of 100 patients at the Saint-Louis Hospital in Paris (Assistance publique – Hôpitaux de Paris), researchers from CEA and Paris-Diderot University have demonstrated that the level of certain immune cells in the blood is a predictor for bladder cancer recurrence and tumor progression. They suggest using this patented blood test to predict recurrence for other types of cancer.

Published on 29 January 2018
HLA-G, a shield that paralyzes the immune system

Molecule HLA-G, Human Leukocyte Antigen, is involved in immune system tolerance, and especially in feto-maternal tolerance. It prevents the fetus from being considered as a foreign element in the organism and thus from being attacked by the immune system. In a healthy organism, this protein is only expressed during pregnancy, on the surface of placental cells. However, it can also be expressed in certain pathologies, as it is the case in transplanted organs or on the surface of tumoral cells.

First tests on heart transplants, carried out in 2002 by Edgardo D. Rosella and his team at the François-Jacob Biology Institute, in Saint-Louis Hospital, and with professor Alain Carpenter in the Broussais Hospital, showed that the expression of HLA-G causes a significant decrease in acute rejection and an absence of chronic rejection. Moreover, the expression of this molecule in tumors is correlated with a bad diagnostic.  If a tumor is not recognized by the immune system, it is not destroyed. Cancer cells use HLA-G to protect themselves from the host's immune defenses, and therefore to grow and recur.

The expression of HLA-G is associated with the evolution of the disease, and therefore, the risks of recurrence and extension. When facing cancer, HLA-G acts as a shield and inhibits the entire immune response.

The CD+ILT2+ count is predictive of bladder tumors recurrence and progression

With the goal of anticipating tumor evolution and reducing the risks of recurrence, professors Edgardo D. Rosella and François Desgrandchamps (St Louis Hospital) have analyzed the expression of HLA-G in bladder tumors, seeking to understand how the immune system can prove defective and allow the tumor to develop. This a true clinical advance since the frequency of bladder cancer is high and has an important immune component, but with no effective treatment.

It turns out that peripheral blood lymphocytes which destruct cancer cells, called CD8 cytotoxic lymphocytes, express at their surface a receptor, called ILT2, whose activation blocks CD8 cells. The study had blood samples from more than 100 patients with bladder cancer that were followed over a three-year period at Saint-Louis Hospital, AP-HP. The findings demonstrate that the recurrence of bladder tumors depends on the percentage of CD8+ ILT2+ cells circulating in the blood.

When patients have a tumor that recurs, more than 40 % of these CD8 lymphocytes carry this receptor. This means that the patient's immune system is weakened regarding the tumor and can be easily inhibited. Based on these findings, the CD8+ILT2+ count makes it possible to identify the patients who have an increased risk of recurrence. Bio-statistical analyses on cohorts of patients consider recurrence as weak if under 20%, and over 40%, as significant.

A patent application has been filed by Assistance publique – Hôpitaux de Paris, Paris Diderot University and CEA for the upcoming development of an evaluation kit. This technology, developed at Saint Louis Hospital, was awarded the 2017 APinnov trophy. This test would benefit from evaluation on a mass scale and on other types of tumors, using the kit developed by professors Carosella and Desgrandchamps. This would be a simple, non-invasive solution for most hospitals and private laboratories, since it relies on a classical technique of flow cytometry from a simple blood draw.

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