5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab

Background

Renal cell carcinoma and melanoma are common cancers with growing incidence rates. Nivolumab, anti-programmed-death 1 protein (PD1) antibody selectively blocks the interaction between PD-1 and its ligand PD-L1 and enables a restart of the immune response against cancer cells, significantly improving survival in both treatment-naïve and pretreated patients with metastatic renal cell carcinoma (mRCC) and metastatic melanoma. It was hypothesized that proliferation of specific T cell clones may be associated with response to anti-PD1 therapy. The aim of this study was to analyze T cell repertoire.

Methods

Blood samples of 10 patients with mRCC and 12 patients with metastatic melanoma were evaluated and compared to 14 healthy controls. All mRCC patients were treated with nivolumab after prior interferon α, sunitinib, pazopanib, everolimus or axitinib. Mononuclear cells were isolated from the peripheral blood on Histopaque. Cells were stained with directly labeled anti-CD3 PerCP-Cy5.5, anti-CD4 APC, anti-CD8 APC-Cy7 and anti-TCR FITC and PE antibodies. In total, 24 Vß TCR families were evaluated. Measurement was performed by multicolor flow cytometry. Data were analyzed with Wilcoxon non-parametric test and principal component analysis.

Results

Significant changes in following TCR families (p < 0.001) were confirmed: an increase of CD4⁺ cells Vß16, Vß20, a decrease of CD4⁺ cells Vß17 and CD8⁺ cells Vß5.1, Vß5.3, Vß7.1, Vß22. In several patients, highly enriched individual populations of CD4⁺ together with CD8⁺ cells were observed. CD4⁺ Vß21.3 was increased significantly in mRCC patients while decreased in melanoma patients.

Conclusions

Significant changes in TCR repertoire were observed in mRCC and melanoma patients treated with nivolumab compared to healthy controls. The changes were different between mRCC and melanoma patients as shown on principal component analysis biplot. Very high levels of CD4 and CD8 lymphocytes with defined TCR Vß families were identified in several patients. Clonal expansion of CD4⁺ and CD8⁺ cells is related to nivolumab treatment and it is likely to correlate with the response to treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.