Tumor mutational burden and immune infiltrates in renal cell carcinoma and matched brain metastases.

BACKGROUND

Tumor mutational burden (TMB) and density of tumor-infiltrating lymphocytes (TIL) have been postulated as predictive biomarkers for immunotherapy. Therefore, we investigated the concordance of TMB and TIL of primary/extracranial renal cell carcinoma (RCC) specimens and matched brain metastases (BM).

PATIENTS AND METHODS

Twenty specimens from 10 patients were retrieved from the Vienna Brain Metastasis Registry (6/10 primary tumor, 4/10 lung metastasis, 10/10 matched BM). TMB was assessed using the TruSight Oncology 500 gene panel with libraries sequenced on a NextSeq instrument. TIL subsets (CD3+, CD8+, CD45RO+, FOXP3+, PD-L1+) were investigated using immunohistochemistry (Ventana Benchmark Ultra system) and automated tissue analysis (Definiens software).

RESULTS

No significant difference in TMB, CD3+, CD8+, CD45RO+, FOXP3+ or PD-L1+ expression was observed between extracranial and matched intracranial specimens (P > 0.05). Higher CD8+ TIL (P = 0.053) and CD45RO+ TIL (P = 0.030) densities in the primary tumor compared with the intracranial samples were observed in specimens collected after exposure to systemic treatment. Neither extracranial sample origin (lung metastasis versus primary RCC) nor extracranial disease status at BM diagnosis (progressive versus stable disease) were significantly associated with TMB or TIL densities in extracranial and intracranial samples (P > 0.05). No significant correlation was found between the median differences of TMB or TIL densities from extracranial to intracranial samples and BM-free survival.

CONCLUSION

The comparable immunological microenvironment of extra- and intracranial tumor samples in our study underscores the immunological activation also in BM from RCC, and therefore, supports the development of immune modulatory treatments also in patients with brain metastatic RCC.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure ASB has research support from Daiichi Sankyo (≤ €10 000), Roche (> €10 000) and honoraria for lectures, consultation or advisory board participation from Roche, Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all < €5000) as well as travel support from Roche, Amgen and AbbVie. GW received restricted travel grants from NX Development Corp. MS received honoraria for ad boards and lectures from Pfizer, Roche, Ipsen, Exelixis, EUSA, Eisai, Alkermes, BMS, MSD and Merck. MP has received research support from Böehringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche and honoraria for lectures, consultation or advisory board participation from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, AstraZeneca, AbbVie, Lilly, MEDahead, Daiichi Sankyo, Merck Sharp & Dome. All other authors have declared no conflicts of interest.