Kidney cancer: discovery of a circulating biomarker predictive of the immunotherapy response

The most common kidney cancer is renal cell carcinoma (about 80% of kidney cancers). Over the past 5 years, the use of immunotherapy for the treatment of metastatic renal cell carcinoma has significantly improved the survival rate of patients with this cancer. However, some patients are resistant to these treatments.

The work of Benhamouda et al, conducted in Prof. E. Tartour’s team (CARPEM team 4), published in the journal Clinical Cancer Research, has identified a mechanism of resistance of renal tumors to immunotherapy.

Tumor cells expressing the CD70 molecule are able to bind to T lymphocytes via the CD27 receptor. This CD70-CD27 interaction leads to the death of T cells by apoptosis, which consequently prevents the immune response in the tumor. The CD27 receptor is then released into the bloodstream in soluble form (sCD27). Interestingly, the level of sCD27 measured in the blood correlated with 1-) the level of CD27-CD70 interaction measured by imaging in the tumor; 2-) the resistance to immunotherapy treatments (using anti-PD1 antibodies).

Together, these results highlight a new mechanism of resistance of these tumors to immunotherapy treatments; and open new therapeutic approaches. The identification of sCD27 as a predictive blood biomarker of response to immunotherapy in metastatic renal cell carcinoma is a major new advance in the management of patients.

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