Assessment of Tumor Microenvironment Inflammatory Biomarkers in Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors.

INTRODUCTION

Therapies using immune checkpoint inhibitors (ICI) are standard of care in metastatic renal cell carcinoma (mRCC). Currently, no accepted standardized biomarkers are available to predict treatment response in mRCC. We aimed to identify the predictive value of immunomodulatory markers interacting within the tumor microenvironment.

PATIENTS AND

METHODS

We included 45 untreated and pretreated patients treated with ICI, divided by their progression free survival (PFS) into groups of good (> 18 months), intermediate (6-18 months) or poor treatment response (< 6 months). Tumor specimens were stained immunohistochemically for 28 markers and analysed by application of digital tissue microarrays using the open source software QuPath.

RESULTS

The phagocytosis checkpoint molecule CD47 significantly predicted and higher CD20 (B cell density) was significantly correlated with longer PFS. CD20 was associated with tumor-infiltrating immune cells and checkpoint molecules.

CONCLUSIONS

Tissue based quantification of CD47 and CD20 might be used to predict response to ICI in mRCC. Both markers influence the anti-tumor response and seem to be markers of a highly immune-infiltrated, and simultaneously functional immunosuppressed TME which seem to profit the most from ICI. Therefore, CD47 and CD20 could be suitable to discriminate between patients which profit from those who would not profit from ICI and avoid unnecessary costs due to side effects.