Abstract 5758
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.
Resources from the same session
1885 - Factors associated with disease progression in patients treated with trametinib in combination with dabrafenib for unresectable advanced BRAFV600-mutant melanoma: an open label, non randomized study
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
5259 - Integrative RNAseq and Target panel sequencing reveals common and distinct innate and adaptive resistance mechanisms to BRAF inhibitors
Presenter: Phil Cheng
Session: Poster Display session 3
Resources:
Abstract
5619 - Effective treatment with T-VEC monotherapy in Stage IIIB/C-IVM1a Melanoma of the Head & Neck Region
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
5666 - Re-introduction of T-VEC Monotherapy in Recurrent Stage IIIB/C-IVM1a melanoma is effective
Presenter: Viola Franke
Session: Poster Display session 3
Resources:
Abstract
4117 - Efficacy of talimogene laherparepvec (T-VEC) in melanoma patients (pts) with locoregional (LR) recurrence, including in-transit metastases (ITM): subgroup analysis of the phase 3 OPTiM study
Presenter: Mark Middleton
Session: Poster Display session 3
Resources:
Abstract
5303 - Real Life Use of Talimogene Laherparepvec in Melanoma in Centers in Austria and Switzeland
Presenter: Christoph Hoeller
Session: Poster Display session 3
Resources:
Abstract
4130 - Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Presenter: Philippe Saiag
Session: Poster Display session 3
Resources:
Abstract
2050 - Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
Presenter: Sarah Knispel
Session: Poster Display session 3
Resources:
Abstract
1618 - Comparative-Effectiveness of Pembrolizumab vs. Nivolumab for Patients with Metastatic Melanoma
Presenter: Justin Moser
Session: Poster Display session 3
Resources:
Abstract
3556 - Long-term efficacy of combination nivolumab and ipilimumab for first-line treatment of advanced melanoma: a network meta-analysis
Presenter: Peter Mohr
Session: Poster Display session 3
Resources:
Abstract