By examining the PD-L1 biomarker in tumour and immune cells under the microscope, doctors gain valuable information on how patients respond to treatments that harness the body’s immune system to fight cancer. (I., 2013)
“Recent advances in immunotherapy are rewriting the book on how we treat cancer and we’re just at the beginning of the first chapter,” explains Dr. Eslie Dennis, Vice President of Medical Affairs at Roche Tissue Diagnostics and a physician with more than 10 years of clinical practice in internal medicine and oncology.
Advanced diagnostics tools are being developed for this new wave of cancer therapies that stimulate the body’s immune system to attack and kill cancer cells.
Why is PD-L1 a useful diagnostic biomarker?
The body’s immune system can mobilise an army of different types of white blood cells to combat attacks not only from bacteria, viruses and fungi, but also from cancer cells. After an attack, the body normally deactivates part of this immune army – the powerful T cells – with the help of a protein known as PD-L1.
This deactivation is normally beneficial. Without it, the immune system could damage healthy cells and tissues. However, some cancer cells actually use this PD-L1 protein to shut down the body’s immune response, essentially camouflaging themselves in a ‘cloak of invisibility.’1
Immunotherapies are now available that block the PD-L1 ‘off switch,’ allowing the immune system to continue recognising and killing cancer cells.
Exposing PD-L1 protein in cells
Diagnostic tests can detect the expression of PD-L1 in a tumor tissue sample, helping doctors make effective use of immunotherapy. Laboratories use a technology – known as immunohistochemistry – that detects and visualises specific proteins in cells to help diagnose diseases like cancer. This technology can demonstrate whether a patient expresses the biomarker PD-L1 on cancer cells, the surrounding immune cells, or both.2
To detect the PD-L1 biomarker, samples of the tumour and surrounding tissue are collected from the patient through a surgical or biopsy procedure. These tissue samples are sent to a pathology lab, where very thin tissue sections are mounted onto glass slides. Antibodies that bind to PD-L1 are applied and a detection system reveals the presence of PD-L1 protein in the tissue sample in the form of a brown stain easily visible under a microscope. “Assessing the percentage of tumour cells and immune cells expressing PD-L1 as well as the distribution of PD-L1 protein in the tissue sample can help doctors determine the potential impact of immunotherapy,” explains Dr. Ehab ElGabry, Roche Companion Diagnostics Head of Pathology. The results allow doctors to make informed decisions for their cancer patients.
“As an oncology physician, I know how crucial it is for patients to start an appropriate therapy as soon as possible,” Eslie says.
Continuing evolution of diagnostic tools
This ongoing focus has led to the development of two different antibody tests to evaluate PD-L1 protein expression in tumour cells and immune cells. Regulatory authorities have already approved these tests for specific types of bladder and lung cancer in some countries, and Roche is exploring their use in more than 20 cancer types.
Innovative technologies and tests help oncologists better understand the role that the body’s immune system plays in the fight against cancer. Among them are tests enabling the simultaneous detection of several different biomarkers on the same microscope slide. Leveraging a technology called multiplexing, these tests show on a cellular level how each patient is reacting to their cancer.
“The goal is to easily and reliably detect multiple markers on a single slide. This will enable better understanding of the tumour microenvironment ‘battlefield’ and aid in identification of critical biomarkers that are driving the immune response,” says Lidija Pestic-Dragovich, Senior Director, Roche Pharma Alliance & Pharma Services.
Lidija adds: “When multiplex technology and sophisticated software algorithms are combined, you have a better understanding of tumour biology. And this greater understanding helps physicians find the best treatment for each individual patient. That’s why multiplex technology is so important to the future of cancer testing.”
This means that patients and physicians have powerful new weapons against cancer both in the laboratory and within the patients’ own bodies.3 With this rapid revolution in diagnostic tools and treatment, a promising chapter in the immunotherapy story is now unfolding.
- Chen DS, et al. Clin Cancer Res. 2012. 18:6580-6587
- Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387:1909-1920.
- Herbst RS, et al. Nature. 2014. 515:563-567