Immunotherapy and age
Recent clinical studies have shown that the blockade of immune checkpoints ("checkpoint blockade", ICB), that is, the activation of the patient's immune system to fight cancer cells, has shown stunning effectiveness in the treatment of breast cancer, especially in terms of the ability to treat patients with triple negative breast cancer. Despite the fact that breast cancer is most often detected over the age of 60, most clinical trials recruit patients under the age of 60. Meanwhile, age may be an important factor in the effectiveness of ICB, given the link between aging and serious changes in the immune system. Therefore, it is too early to talk about the effectiveness of ICB therapy for patients of all age groups.
To understand the impact of aging on the effectiveness of ICB, researchers from Brigham and Women's Hospital (Brigham and Women's Hospital), the Institute of Oncology named after Dana-Farber and Harvard Medical School conducted preclinical studies on young and elderly mice with a model of triple negative breast cancer and found that age affects the effectiveness of therapy by blocking immune control points.
The researchers injected triple negative breast cancer cell lines into young (8-12 weeks old) and old (12-15 months old) mice. As soon as palpable tumors appeared, the mice were given four doses of one of two drugs – antibodies to proteins that suppress the immune system, PD-L1 or CTLA-4. One group of mice received control antibodies. The researchers then measured and evaluated changes in the tumor over time.
The study proved that age affects the body's response to immunotherapy. The young mice showed a significant reduction in tumor growth and a better overall survival in response to treatment than those who did not receive treatment. Immunotherapy did not bring significant benefits to older mice compared to mice from the control group.
The researchers also examined the METABRIC database, which contains information about tumor samples from patients with triple negative breast cancer. Gene markers that were responsible for sensitivity to ICB in young mice were found in samples from young patients and were absent in the elderly. Signs were found indicating the insufficiency of the innate immune system in tumors both in old mice and in tumor samples of elderly patients with triple negative breast cancer. So the researchers came to the conclusion that the results obtained in mice may also be relevant to the treatment of humans.
The group tested a new type of combination therapy: a drug for ICB together with an agonist of the stimulator of interferon genes, which has the properties of immunoactivation. As a result of treatment, the tumors of old mice responded to ICB, and survival improved.
Thus, the assessment of changes occurring in the immune system with age could become a new way of understanding immunotherapy. The immunological age may not coincide with the chronological age, and this shows the need to use markers of immunological age, making it possible to take it into account for making decisions about the patient's treatment tactics.
Article by J. Sceneay et al. Interferon Signaling is Diminished with Age and is Associated with Immune Checkpoint Blockade Efficacy in Triple-Negative Breast Cancer published in the journal Cancer Discovery.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Brigham and Women's Hospital: Preclinical Study Reveals the Impact of Age on Immunotherapy Treatment for Breast Cancer.