Clinical trial reveals better response to nasopharyngeal cancer treatment with anti-PD1 blockade and chemotherapy in COVID-vaccinated patients
Therapeutic use of checkpoint inhibitors, targeting anti-programmed cell death protein 1 (PD-1), is common in the treatment of nasopharyngeal cancer. Until now, it was feared that vaccination against SarsCoV-2 could reduce the success of anti-PD-1 treatment or cause severe side effects. A recent study by scientists of ImmunoSensation2 at the University of Bonn, together with colleagues at the University of Shanxi in the People's Republic of China now gives the all-clear in this regard. According to the study, the cancer drugs actually worked better after vaccination with the Chinese vaccine SinoVac than in unvaccinated patients. The results are published as a "Letter to the editor" in the journal Annals of Oncology, but are already available online.
Immune checkpoints allow the immune system to differentiate between self and non-self. Anti-programmed cell death protein 1 (PD-1) serves as a checkpoint protein on the surface of T-Cells. Binding of PD-1 ligand (PD-1-L1) to PD-1 effectively shuts down an immune response. By expressing PD-1-L1 on the cell surface, many cancer cells are capable of subverting the body’s immune response. In order to restore immune function in the tumor microenvironment, checkpoint inhibitory drugs blocking PD-1 or PD-1-L1 are widely used.
Vaccination against SarsCoV-2 also stimulates the immune response, involving the PD-1 receptor. "It was feared that the vaccine would not be compatible with anti-PD-1 therapy," explains Dr. Jian Li of the Institute of Molecular Medicine and Experimental Immunology (IMMEI) at the University Hospital Bonn. "This risk is especially true for nasopharyngeal cancer, which, like the SARS Cov-2 virus, affects the upper respiratory tract."
Together with cooperation partners from the People's Republic of China, the bioinformatician has now investigated whether this concern is justified. More than 1,500 patients treated in 23 hospitals from all over China participated in the analysis. Such multi-center studies are considered to be particularly informative because the participants are very diverse and, moreover, the results are not distorted by regional characteristics.
Vaccinated patients responded better to cancer therapy
A subset of 373 affected individuals had been vaccinated with the Chinese Covid vaccine SinoVac. "Surprisingly, they responded significantly better to anti-PD-1 therapy than the unvaccinated patients," explains Prof. Dr. Christian Kurts, Director of the IMMEI at the University Clinics Bonn and member of the Transdisciplinary Research Area "Life & Health". "Furthermore, they did not experience severe side effects more often."
The researchers cannot say why the treatment was more successful after vaccination. "We assume that vaccination activates certain immune cells, which then attack the tumor," says Prof. Dr. Qi Mei of Shanxi University Hospital. "We will now investigate this hypothesis further."
Nasopharyngeal cancer is quite rare in western countries. In southern China and other countries in Southeast Asia, however, the disease is widespread. One of the suspected reasons for this is the frequent use of air conditioning in the hot and humid regions. Nutritional factors also appear to play an important role. In Taiwan, nasopharyngeal cancer is now considered one of the leading causes of death among young men.
Funding
In addition to the University of Bonn and the University Hospital, Shanxi Medical University and Tongji Medical College were involved in the work. The researchers also collaborated with a number of clinics throughout China. The study was funded by the Sino-German Center for Research Promotion (SGC), the DFG Cluster of Excellence ImmunoSensation², and the German Federal Ministry of Education and Research (BMBF).
Publication
Hua YJ, Liu YL, Wen K, Kurts C, Wu H, Mei Q, Li J, Potentially Improved Response of COVID-19 vaccinated Nasopharyngeal Cancer Patients to Combination Therapy with Anti-PD-1 Blockade and Chemotherapy, Annals of Oncology (2022), DOI: 10.1016/j.annonc.2022.10.002
Contact
Dr. Jian Li
Institute of Molecular Medicine and Experimental Immunology (IMMEI)
University Hospital Bonn
Phone +49 (0) 228/287-51050
Email: jianli@uni-bonn.de
