Severe COVID-19 course with cancer: Impaired immune response may be the cause

Patients with cancer who are infected with the coronavirus have an increased risk of severe COVID-19 disease.

Antibody response against SARS-CoV-2 in tumor patients comparable to that of COVID-19 recovered patients without cancer

Patients with cancer who are infected with the coronavirus have an increased risk of severe COVID-19 disease. A new study by the Clinical Cooperation Unit for Translational Immunology (Klinische Kooperationseinheit Translationale Immunologie) and the Department of Immunology at the University Hospital Tübingen and the Robert Bosch Centre for Tumor Diseases (Robert Bosch Centrum für Tumor-erkrankungen, RBCT) in Stuttgart now shows that a limited immune response, caused by the cancer itself or the cancer therapy, can be the reason for this. With the help of these new findings, the research team has developed a vaccine that is intended to induce a targeted T cell response against the coronavirus in cancer patients.

Cancer patients, especially those with malignant diseases of the blood and lymphatic system such as leukaemia or lymphoma, are at increased risk of a more severe course of disease if they are infected with the coronavirus. The new study suggests that one possible reason for this could be a limited immune response, which in tumor patients is caused by the disease itself and/or the cancer therapy. "The formation of an immune response after an infection with SARS-CoV-2 or a prophylactic vaccination is essential for protection against the COVID-19 disease and ultimately for the development of long-term immunity," explains Dr. Juliane Walz. Two components of the immune system play a decisive role in the development of immunity: The B cells, which form antibodies that can neutralise the virus, and the T cells, which destroy virus-infected cells and support the formation of antibodies. Dr. Walz's research group has investigated the immune responses against SARS-CoV-2 in tumor patients and gained important insights into the pathophysiology and for predicting the severity of the viral disease. These will enable the development of targeted therapeutic interventions and vaccines for this vulnerable patient population.

For the research, which was funded by the COVID-19 special funding measure of the German Federal Ministry of Education and Research, cancer patients with a SARS-CoV-2 infection were studied and the immune response against the virus was compared with that of those who had recovered. "We were able to show that the antibody response against SARS-CoV-2 in tumor patients is comparable to that of COVID-19 recovered patients without cancer. In contrast, however, tumor patients - and in particular people with cancers of the blood and lymphatic system - show significantly weaker and less frequent T cell responses against SARS-CoV-2. Similarly, the T cells of tumor patients recognise fewer different components of the coronavirus. This reduced so-called diversity of T cell response is associated with a severe course of COVID-19 disease in tumor patients," said Dr. Walz.

Working on SARS-CoV-2 vaccine to specifically induce a T cell response in cancer patients

In addition, the study, which was conducted in cooperation with the Departments of Haematology and Oncology in Tübingen and Bonn as well as the Department of Gynaecology, the Department of Dermatology and the Department of Urology at the University Hospital in Tübingen, examined blood samples from cancer patients that were collected before the outbreak of the pandemic and thus had no contact with SARS-CoV-2. In preliminary work, the Tübingen researchers were already able to show that cross-reactive T cells against SARS-CoV-2 are present in up to 81% of healthy donors due to previous contact with other human common cold coronaviruses. Such cross-reactive T cell responses are thought to provide some protection against SARS-CoV-2 and COVID-19 disease. The Tübingen research group has now found that not only the SARS-CoV-2 specific T cell response, but also these cross-reactive T cell responses are significantly reduced in patients with leukaemia and lymphoma. This is due to a general exhaustion of the T cell response in these patients, which is also reflected by reduced T cell responses against other viral diseases.

Based on the findings of this study, the Clinical Cooperation Unit for Translational Immunology team (Medical Director: Prof. Dr. Helmut Salih) together with the Department of Immunology (Director: Prof. Dr. Hans-Georg Rammensee) in Tübingen is establishing a clinical trial that will soon use a SARS-CoV-2 vaccine for the targeted induction of a T cell response in cancer patients. The vaccine (CoVac-1) has already been evaluated in a first study in healthy subjects; preliminary results show that very strong T cell responses can be generated with this vaccine.

1. Preexisting and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients.
Tatjana Bilich, Malte Roerden, Yacine Maringer, Annika Nelde, Jonas S Heitmann, Marissa L Dubbelaar, Andreas Peter, Sebastian Horber, Jens Bauer, Jonas Rieth, Marcel Wacker, Fiamma Berner, Lukas Flatz, Stefanie Held, Peter Brossart, Melanie Marklin, Philipp Wagner, Eva Erne, Reinhild Klein, Hans-Georg Rammensee, Helmut R Salih and Juliane S. Walz
Cancer Discov May 19 2021 DOI: 10.1158/2159-8290.CD-21-0191