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Certain patients with bladder cancer are treated by instilling the bladder with the BCG vaccine. This treatment leads to a more active innate immune system and reduces the risk of respiratory infections. This ’training’ of the immune system potentially also increases the effectiveness of bladder cancer treatment, according to a study performed by Radboud university medical center.
Every year, approximately 7,000 Dutch people are diagnosed with bladder cancer. If the tumor has progressed into the muscle layer of the bladder, the entire bladder often has to be surgically removed. If not, removal of only the tumor followed by instilling the bladder with medication suffices. One of the drugs used for this purpose is BCG. This vaccine, originally developed against tuberculosis, has been used to treat bladder cancer since the 1970s. It thereby is the oldest form of immunotherapy for cancer. More than a decade ago, researchers at Radboud university medical center discovered that vaccination with BCG ‘trains’ the innate immune system. As a result, the vaccine also protects against infections other than tuberculosis. It now appears that bladder instillations with BCG also train the innate immune system.
Fewer infections
'The innate immune system of bladder cancer patients was more active after BCG instillations than before,' says first author Jelmer van Puffelen, who works in the departments of Health Evidence and Internal Medicine at Radboud university medical center. Among other things, he showed that immune cells of these patients produced more signaling proteins after instillations. This effect persisted for months after the last instillation. The study also shows that this training of the immune system is beneficial for patients. Van Puffelen: ‘BCG reduced the risk of respiratory infections by a third. So, similar to vaccination with BCG, bladder instillations with this vaccine appear to provide broad protection against infections.'
Cancer-free for longer
The study also shows a link between training of the innate immune system and the effectiveness of BCG instillations in bladder cancer. To explore this, the researchers looked at variation in genes that were previously shown to be associated with the degree of training after BCG vaccination. Research leader Sita Vermeulen of the department for Health Evidence explains: ‘Individuals with certain genetic variants respond more strongly to BCG; their immune system is trained more effectively. In patients with these variants, bladder cancer returned less quickly and less often than in patients with genetic variants that are associated with less efficient BCG training.'
Combination therapy
Will this study change the treatment of bladder cancer? 'Now that we know that training of the immune system may be important in these patients, we can explore even more effective therapies’, says Vermeulen. 'These include combinations of BCG with other drugs that enhance the training effect. Or a genetically modified form of the BCG vaccine that induces stronger training. We are studying how effective these new strategies are, but this is still in an experimental phase.'
About the publication
This study was published in the Journal for ImmunoTherapy of Cancer: Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections. Jelmer H van Puffelen, Boris Novakovic, Liesbeth van Emst, Denise Kooper, Tahlita C.M. Zuiverloon, Ursula T.H. Oldenhof, J. Alfred Witjes, Tessel E. Galesloot, Alina Vrieling, Katja K.H. Aben, Lambertus A.L.M. Kiemeney, Egbert Oosterwijk, Mihai G. Netea, Joost L. Boormans, Antoine G. van der Heijden, Leo A.B. Joosten, Sita H. Vermeulen. DOI: 10.1136/jitc-2022-005518.
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