In the past decade, scientists were intrigued by the potential of utilizing the body's immune system to target and attack cancer cells. This revolutionary immunotherapy idea showed great promise, especially when it offered precise targeting of cancer cells, an alternative to the current non-specific therapies such as chemotherapy and radiation. One of the challenges of immunotherapy is to target the elusive cancer cells and block the molecular signaling that makes them invisible to the immune system. One way the cancer cells live and multiply undetected by the immune system is by expressing proteins on their cell membrane that bind to PD-1 and CTLA-4, two receptors on T cells that negatively regulate T cell activation. PD-1 and CTLA-4 act as a type of "off switch" to make the T cells inactive which help to regulate the immune system. One class of cancer immunotherapy drugs, known as checkpoint blockade inhibitors, disables either PD-1 or CTLA-4 receptors, so the cancer cells won't be able to switch them off.
The clinical responsiveness to this class of drugs superseded doctors' expectation, but it only worked in some patients. The results varied considerably between patients and treatment was considered successful in only 30% of the patients.
The molecular basis for the responsiveness variation remained unclear until a recent discovery by scientists at the University of Southampton and La Jolla Institute for Allergy & Immunology, California.
The Scientists identified a new type of subpopulation of T cell, Tissue-Resident Memory T Cell (TRM cell). The scientific discovery emerged from analysis of large-scale gene expression patterns of cytotoxic T cells isolated directly from 689 lung cancer patients' tumors.
The study results that were recently published in Nature Immunology showed that lung cancer patients with many Tissue-Resident Memory T cells infiltrating the tumors were 34% less likely to die than others.
The recently identified TRM cells act as local first responders that provide rapid onsite immune protection.
These new T-cells produce molecules that attack the tumor and enhance cytotoxicity which makes the tumor cells more vulnerable to the immune system.
This discovery could guide who will benefit from the immunotherapy drugs and predict the effectiveness of the treatment. Utilizing this discovery as a screening method may reduce patient's side effects and will also ultimately reduce health costs. This discovery brings us one step closer to a tailored treatment to the patient, also known as personalized medicine (or precision medicine).
Another potential application of this discovery is to use TRM-cells as a way to enhance immunotherapy by using these cells as a template to develop a vaccine to boost the immune responsiveness and by that tackle even the hardest to treat cancers.
According to the American Cancer Association, Lung cancer is the leading cause of cancer death among both men and women. There are 22,500 new cases of lung cancer each year and about 155,870 deaths from lung cancer. Immunotherapy drugs are expected to generate tens of billions of dollars in annual sales by early next decade, with lung cancer the biggest single market.