Protein in bladder cancer is used to predict recurrence

Protein in bladder cancer is used to predict recurrence Bladder cancer is a common disease which affects 6 people per 100,000. It is hard to predict its progression and recurrence. A protein called PD-L1 is essential in certain types of bladder cancer. Sechenov University scientists have studied the molecule’s role in non-muscle invasive bladder cancer and discovered its association with tumour types and treatment history.

Some types of cancer have very unpredictable progression, treatment outcome, and recurrence. Non-muscle invasive bladder cancer (NMIBC) is one of such diseases. Currently, the simple stratification based on tumour type or grade is unable to estimate the possible efficacy of chemotherapy and/or immunotherapy. An immune protein called PD-L1 plays a crucial role in the treatment of muscle-invasive bladder cancers (MIBC), but not much is known about its role in NMIBC. A team of scientists, led by Sechenov University members, has analysed the association of this molecule with non-muscle invasive bladder cancer and published their report in the journal Cancers.

PD-L1, which stands for programmed death receptor ligand 1, is the best-studied immune checkpoint molecule that promotes immunosuppression. The Bacillus Calmette–Guérin (BCG) vaccine, widely used for the prevention of tuberculosis, is also known to have an immunotherapeutic effect in bladder cancers. In fact, BCG has been the gold standard for the treatment of NMIBC since the 1970s, although the mechanism of its action remains unclear. The study has focused on the relationship between PD-L1 expression and BCG immunotherapy, as well as the use of PD-L1 expression for prognosis — in combination with other molecular and genetic markers.

The researchers found that the first basal and luminal relapses of NMIBC are characterised by the upregulation of PD-L1, except in the case of low-grade basal mitomycin-treated NMIBC. It did not depend on the tumour grade or preceding therapy. In contrast, the high-grade double-negative p53-mutant recurrent NMIBC showed differential expression of PD-L1 that was determined by the previous treatment, and low-grade double-negative relapsed bladder tumours always had a low level of PD-L1 or tested negative for it.

All tested tumour subtypes were infiltrated by PD-L1-expressing CD8+ cytotoxic cells in chemotherapy- and immunotherapy-naive high- and low-grade relapsed luminal and basal NMIBC, and in high- and low-grade luminal and double-negative, high-grade basal relapsed urothelial carcinoma after previous immunotherapy by BCG.

Finally, the research showed that PD-L1 expression in recurrent NMIBC is associated not only with the tumour grade but also with its molecular subtype and previously used frontline treatment. Targeting the PD-L1 pathway can be a very useful strategy to control the disease effectively.

‘Biological therapy and immunotherapy of malignant tumours are a breakthrough in oncology that allowed us to effectively fight cancer and extend the patient’s life’, commented Ekaterina Blinova, Professor at the Department of Clinical Anatomy and Operative Surgery (Sechenov University) and the first author of the paper. ‘However, genetic and molecular non-uniformity of the tumours originating from the same tissue at different stages has an impact on the response to biological therapy and the survival rate. In this work, we have shown the molecular variants of non-muscle invasive bladder cancer where the use of contemporary treatment approaches allows us to achieve the best effect and slow down the recurrence of the disease’.

The study, supported by the Russian academic excellence project ‘5–100’, was carried out by Sechenov University (Department of Clinical Anatomy and Operative Surgery, Department of Pathological Anatomy, Institute for Urology and Reproductive Health) in collaboration with several other Russian research organisations.

Read more: Blinova E, Enikeev D, et al. Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy. Cancers (2020).

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