Lung cancer: the leading cause of cancer death
Lung cancer is the most common cancer worldwide and the leading cause of all
cancer-related deaths, responsible for approximately 1 in 5 cancer deaths.3 More people die from lung cancer than from colon, breast, and prostate cancers combined.3,67 Advances have been made in the management of metastatic lung cancer over the past 2 decades, but prognosis remains poor and improvement in survival in a broad patient population has been limited.3,68 There is a critical need for more effective treatment options for patients with lung cancer.
- Over 1.8 million new cases of lung cancer are diagnosed worldwide each year3
- There are nearly 1.6 million deaths annually3
The immune system’s response to lung cancer cells
The immune system is complex, made up of multiple mechanisms that act to protect and defend the human body. In a normal state, the immune system can recognize cancer cells as abnormal and mount a defense through a process called immune surveillance. During what is called an antitumor response, immune cells, including activated T cells, can recognize the tumor and eliminate tumor cells from the body.11-14 There is clinical evidence that the immune system can naturally react to and destroy lung cancer cells:
- T cells can recognize lung cancer cells as abnormal through specific proteins known as “tumor-associated antigens” expressed on the surface of the tumor cell10,69
- Lung cancer specimens from patients show evidence of an immune response against tumors70
- The presence of various immune cells, including T cells, in the tumor environment have been associated with longer overall survival and disease-free survival for lung cancer patients44,71
Tumor immune evasion through checkpoint pathways
During the multistep development of lung cancer, tumor cells may adapt to escape the immune system’s defense mechanisms, which can lead to evasion of immune destruction and to tumor growth.15,16,22 The ability to evade immune destruction is an emerging hallmark of cancer.64
Research indicates that tumors may evade cytotoxic (“killer”) T cells in part by exploiting immune activation and inhibition pathways—essentially “switching off” immune activation and response.11,15,16
Inhibitory checkpoint pathways can modulate T-cell activity to protect the body from being attacked by its own immune system. Several of these pathways are targets of clinical research for their role in tumor evasion of the immune system.11,16 This includes the CTLA-4 (cytotoxic T-lymphocyte antigen 4) pathway, the PD-1 (programmed death-1) pathway, PD-L1 (programmed cell death 1 ligand 1) pathway, and the LAG-3 (anti-lymphocyte activation gene-3) pathway.72-75
The potential for I-O (Immuno-Oncology) in lung cancer
The mechanisms by which lung cancer cells escape the immune system are an increased area of focus. The importance of immune checkpoint pathways has been highlighted by research into the role of the immune system in lung cancer.11,16 Understanding how pathways can be modulated to overcome tumor evasion of the immune system is an active focus of clinical research.76 Patient data show that the immune system may play a role in tumor control in lung cancer.44,71,77,78
Immuno-Oncology (I-O) is an evolving treatment modality designed to harness the natural capability of the patient’s own immune system to fight cancer.2 Immuno-Oncology (I-O) is providing insights into understanding the immune system’s role in cancer and how tumors evade recognition and attack.8,9
At Bristol-Myers Squibb, we are researching novel immunotherapies that may modulate the immune system with the aim of enhancing the antitumor immune response. We are committed to advancing current standards of care for patients with lung cancer. Our research is focused on restoring the way the immune system interacts with and responds to the tumor cell.
By finding new ways to stop lung cancer cells from evading the immune system, Immuno-Oncology (I-O) therapy may be able to help restore the body’s natural ability to fight it.