1164P - Changes of TCR repertoire in metastatic melanoma and renal cell carcinoma patients treated with nivolumab correlate with overall survival

Background

Melanoma and renal cell carcinoma 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 patients with metastatic melanoma and metastatic renal cell carcinoma (mRCC). 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 in metastatic melanoma and mRCC patients treated with nivolumab and to correlate in with disease progression and overall survival.

Methods

Blood samples of 35 patients with metastatic melanoma and 21 patients with mRCC were evaluated and compared to 14 healthy controls. All melanoma patients were treated in 1^st or 2^nd line with nivolumab, all mRCC patients were treated with nivolumab in 2^nd to 5^th line 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 Vβ 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 several TCR families (p<0.001) were confirmed: an increase of CD4⁺ cells or an increase of CD8⁺ cells were observed. In several patients, highly enriched individual populations of CD4⁺Vβ or CD8⁺Vβ cells were observed (>10% of CD3⁺). In these patients, median overall survival (OS) in 5 year observation was not reached, while in patients who did not show enriched Vβ cells, median OS was 3.15 years.

Conclusions

Significant changes in TCR repertoire were observed in melanoma and mRCC patients treated with nivolumab compared to healthy controls. Very high levels of CD4 and CD8 lymphocytes with defined TCR Vβ families were identified in approximately 40% of patients. Clonal expansion of CD4⁺ and CD8⁺ cells correlates with the response to treatment and overall survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Palacky University in Olomouc.

Disclosure

All authors have declared no conflicts of interest.