Abstract 5543
Background
Evidence suggests that ATB and gut microbiota composition are associated to anti-PD-1 outcomes in RCC patients. Network analysis of the gut microbiota represents a novel tool to determine “guilds” of bacterial communities.
Methods
Here, we investigated guilds’ relationships with prior exposure to ATB, TKI [axitinib (axi), sunitinib (suni) or other] and clinical outcomes of RCC patients treated with nivolumab (nivo).
Results
Considering prior exposure to ATB (n = 11, 22%), axi (n = 13, 19%), suni (n = 49, 71%) or other TKI (n = 20, 29%), n = 36 (52%) patients were NR and 33 (48%) R to nivo. Cross-validation of overall fecal microbiota composition stratified RCC patients with different predictive power (ATB=84%; axi=81%; suni=69%; outcome=49%). Network analysis revealed six guilds (G1 to G6). G1-G2 behaved in an opposite way and topologically separated by negative correlations. G1-G2 were both related to NR, while G1 was dominated by species related to ATB. Conversely G2 was mainly represented by species related to no ATB (X2=8.98, P = 0.0027) and more susceptible to prior TKI exposure (where axi and suni behaved in an opposite way) compared to the other guilds (X2=10.68, P = 0.0011). G4 was mainly inhabited by species related to other TKI (no axi and no suni). Random forest analysis found definite bacterial species able to drive the stratification into guilds of the global RCC network, such as Akkermansia muciniphila for R and Dorea formicigenerans for no ATB.
Conclusions
We show that ATB and suni are the most powerful external features able to drive fecal microbiota compositional shifts in RCC patients treated with nivo. Analysis of the gut microbiota using bacterial communities guilds provides a novel theranostic approach to stratify RCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Albiges: Honoraria (self): Novartis, BMS, Amgen, Ipsen, Roche, Pfizer, Astellas, Merck. K. Fizazi: Advisory / Consultancy: Participation to advisory boards/honorarium for: Astellas, AAA, Bayer, Clovis, Curevac, Incyte, Janssen, MSD, Orion, Sanofi. B. Escudier: Advisory / Consultancy: IPSEN, BMS, AZ, Novartis, Roche, Oncorena. L. Zitvogel: Advisory / Consultancy: BMS, AstraZeneca,; Research grant / Funding (self): Incyte, GSK, Transgene, Innovate Biopharma, Pilege; Advisory / Consultancy: Everimmune. All other authors have declared no conflicts of interest.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract