Abstract 3988
Background
PD-1 blockade on Regulatory T cells (Tregs) increases resistance of effector T cells to Tregs suppression and directly reduces in vitro Tregs suppressive function. NKs expressed PD-1 and engagement of PD-1 reduces their cytolysis potential. and the effect of CXCR4 antagonism are evaluated on ex vivo Tregs and NKs.
Methods
43 Nivolumab treated-mRCC patients, 20 other than ICI treated –mRCC (CTR) and 15 Healthy donors (HD) were enrolled. 29 patients underwent first clinical evaluation at 3 months resulting in 23 patients with Objective Response (OR) and 6 in progression (PD). Tregs (CD4+CD25+CD127lowFOXP3+) and NKs (CD3-CD56+CD107a+) phenotype and function were evaluated at day 0, 14, 28, 90, and 180. CFSE-T-effector proliferation-Treg dependent and CD107a externalization toward K562 as NK function were evaluated.
Results
29 patients underwent first clinical evaluation at 3 months resulting in 23 patients with Objective Response (OR) and 6 in progression (PD). Higher NKG2D was reported on CD3-CD56dim cells from OR patients as compared to PD patients (p = 0.0054). A clear reduction in NK basal activity was detected at T0 in 3 months progressed Nivolumab treated patients (p = 0.029). Percent of basal Tregs CD4+CD25+CD127lowFOXP3+ was robustly high (p < 0.001) and CD8/Tregs ratio low (p < 0.001) in 63 mRCC patients as compared to 15 HD. Significant lower PD-1 in Treg cells was observed at 3 months treatment in OR patients ( p = 0.048) and a decrease of HELIOS was showed in PD vs OR patients at time 0 (p = 0.017). Ex vivo Tregs were significantly inhibited by CXCR4 antagonism at day 14 in OR patients (p = 0.0024). Characterization of primary RCCs tumor microenvironment and proteomic/ cyto-chemokines profile are ongoing.
Conclusions
Basal NK activity and early detection (2 weeks) of CXCR4 dependent reversal of Treg suppressive activity significantly discriminates mRCC Nivolumab responding patients.
Clinical trial identification
NCT03891485.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Transcan 2016.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5218 - Elevated driver mutational burden or number of perturbed pathways and poor response to abiraterone or enzalutamide in metastatic castration-resistant prostate cancer
Presenter: Bram De Laere
Session: Poster Display session 3
Resources:
Abstract
2452 - High proportion of multiple KRAS mutations in circulating tumor DNA and tumor tissue of pancreatic ductal adenocarcinoma
Presenter: Min Kyeong Kim
Session: Poster Display session 3
Resources:
Abstract
3328 - Biological difference of tumor mutational burden (TMB) and microsatellite instability (MSI) status in patients (pts) with somatic vs. germline BRCA1/2-mutated advanced gastrointestinal (GI) cancers using cell-free DNA (cfDNA) sequencing analysis in the GOZILA study
Presenter: Yasuyuki Kawamoto
Session: Poster Display session 3
Resources:
Abstract
3022 - Cell-Free DNA to Detect Focal Versus Non-Focal MET Amplification in Metastatic Colorectal Cancer Patients: Combined Analysis from Japan and the United States
Presenter: Mishima Saori
Session: Poster Display session 3
Resources:
Abstract
2833 - Presence of circulating tumor DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis
Presenter: Andres Correa
Session: Poster Display session 3
Resources:
Abstract
1376 - Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer
Presenter: Junghee Lee
Session: Poster Display session 3
Resources:
Abstract
4050 - DEMo: a prospective evaluation of a prognostic clinico-molecular composite score in NSCLC patients treated with immunotherapy.
Presenter: Arsela Prelaj
Session: Poster Display session 3
Resources:
Abstract
4727 - Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single agent pembrolizumab (P)
Presenter: Cindy Yang
Session: Poster Display session 3
Resources:
Abstract
3662 - Dynamic changes in whole-genome cell-free DNA (cfDNA) to identify disease progression prior to imaging in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3817 - Evaluation of Microsatellite Instability Testing Through cell-free DNA sequencing
Presenter: Shile Zhang
Session: Poster Display session 3
Resources:
Abstract