News article: New approach developed to predict response of immunotherapies in lung cancer

At the end of last year, Clemens Hinterleitner and Lars Zender published their study "Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer" in Nature Communications. The research group was able to develop a new methodology to better predict the likelihood of success of immunotherapies in lung cancer. An article on this topic appeared last weekend in the Stuttgarter Zeitung and Nachrichten:

Blood test reveals success of cancer therapy

More and more immunotherapies are being used to better treat lung cancer. But the therapy does not work well for everyone affected. To better assess the chances of success, oncologists from Tübingen have now developed a test.

The persistent coughing made him wonder. Throughout his life, Apostolos Valuxidis has been what is known in Swabian as a "man of action". Originally from Greece, he has long since made a new home here in Baden-Württemberg. He lives in Reutlingen with his wife and two children, and has a good job with a manufacturer of plastic packaging. "It could have just continued like this," says the 55-year-old.

If it hadn't been for that persistent dry cough: Probably bronchitis, the family doctor said, and sent Valuxidis to a pulmonary specialist. He found no abnormal findings, but made an appointment with a radiologist just to be on the safe side. A computed tomography (CT) scan at the end of 2021 finally revealed the cause: a 0.8-inch-long tumor in his chest. The cancer had already spread into the body. A cure by surgery is not possible.

Such a diagnosis triggers mortal fears in most people. For many years, even in medical circles, it was considered a success when lung cancer patients were able to extend their lives by a few months with the help of chemotherapy. In the meantime, however, more and more possibilities are being discovered to treat bronchial carcinomas with targeted drugs or immunotherapies. These enable the patient's body's defenses to recognize the tumor cells and fight them effectively. Immunotherapies with so-called checkpoint inhibitors are particularly promising in this respect: they counteract a mechanism by which tumors evade the killer cells of the immune system.

However, in some patients these drugs are not effective or not effective enough. For example, the long-term response rate in patients with non-small cell lung cancer - the most common form of lung cancer - ranges between 15 and 20 percent.

To find out for which patient this form of immunotherapy is suitable, a tissue sample of the tumor is taken by bronchoscopy. The cancer cells are then examined for certain surface molecules - usually the protein PD-L1, which the tumor cell uses to interrupt one of the complex signaling pathways in the immune defense system.

Valuxidis also had a tissue sample taken. "Chemotherapy didn't work for me." At the University Hospital in Tübingen, he was also suggested immunotherapy with checkpoint inhibitors. The results of the biopsy had shown that this treatment held a certain chance of success.

In fact, this preliminary examination is not always considered reliable by experts: "The problem is that tumors are very heterogeneous and that a single biopsy does not adequately reflect the totality of the tumor," says Lars Zender, Medical Director of the Department of Medical Oncology and Pneumology at the University Hospital of Tübingen, for example. It cannot be determined with certainty whether sufficient PD-L1 molecules are present on the tumor cells to be able to assess whether immunotherapy with checkpoint inhibitors is promising.

At Tübingen University Hospital, one of the 2020 newly selected sites of the National Center for Tumor Diseases (NCT), oncologists led by Lars Zender and his colleague Clemens Hinterleitner have therefore been working on a safe alternative for some time. Both are conducting research in the only oncological excellence cluster "iFIT" in Tübingen to develop new and innovative cancer therapies. Their goal is to bring a blood test to market that will replace tissue sampling: "We have discovered that certain components in the blood - the platelets - are able to take up proteins from other cells with which they come into contact," says Hinterleitner.

This includes the surface protein PD-L1 of tumor cells. After all, platelets flow through tumor tissue several hundred times a day. "A blood sample is therefore sufficient to find out the individual PD-L1 level and also to check it regularly," Hinterleitner says. As the Tübingen oncologists report in the journal Nature Communications, this individual value is an ideal indicator of whether the desired immune response with the checkpoint inhibitors is effective - and how long the treatment is useful.

A prospective multicenter clinical trial is still needed to solidify the findings to date. This is currently being prepared, says Zender, oncologist and spokesperson of the iFIT Cluster of Excellence.

Lung cancer patients like Valuxidis hope for quick results: "Just the fact that doctors can predict with certainty how good the chances of success of a therapy are, helps sufferers a lot," he is sure. In his own case, the tissue sample did not promise too much: since starting antibody therapy in early summer, the metastases and the cancerous tumor in his lungs have become smaller. He has always been confident, Valuxidis says. "I'm living my life." That's what counts, he says, not the cancer.

Excellent Research

Lung Cancer. In Germany, around 57,000 people are diagnosed with lung cancer each year. The technical word for lung cancer is bronchial carcinoma. Experts distinguish between non-small cell lung cancer (abbreviated: NSCLC) and small cell lung cancer (SCLC).

Cluster of Excellence. With the so-called "Clusters of Excellence", internationally competitive research fields at German universities and university networks are funded on a project basis by the federal and state governments in order to strengthen top-level research. Among them also the University of Tübingen.

Check out the video for more information on the study: https://www.youtube.com/watch?v=cg5_BoznBEQ&list=PLjQMEeEDuy2sFs4-FpQ-rjEpYWfkBZ8Qs&index=6