Abstract 581P
Background
T-cell–inflammation gene-expression profiling (GEP), programmed death-ligand 1 (PD-L1) expression, and tumour mutational burden (TMB) have been proposed as predictive biomarkers to anti-PD-1/PD-L1 immune checkpoint inhibitors (ICI). While TMB and PD-L1 have a widespread implementation in early clinical trial reference centers, the more novel GEP is lagging behind. We have developed the VIGex gene panel, a gene set selected for immune profiling and subtyping of patients. The panel includes 51 different genes, allowing detection of an immune activation signature consistent with interferon-γ signaling (CXCL9-11, GZMB, IFNG), along with indicators of immunosuppressive processes: T-cell exhaustion markers (CTLA4 or CD274), presence of Tregs (FOXP3), tumour associated macrophages (TAM) (MRC1, CD163) as well as antiinflammatory cytokines (IL10, IL11, TGFB1-3).
Methods
RNA analysis using the VIGex panel was performed on 638 FFPE tumour samples. The most frequent tumour types in our series were CRC (n=155), pancreas (n=130), NSCLC (n=74), gastric (n=45) and CNS (n=41). Gene expression analysis was performed using Nanostring nCounter and analyzed with nSolver software and R in-house scripts. After intra- and inter-run normalization, an unsupervised hierarchical clustering with Ward’s minimum variance method and correlation-based distance was performed. Tumour infiltrating lymphocytes (TILs) were evaluated by a pathologist in a subset of the samples (n=40).
Results
Unsupervised hierarchical clustering analysis revealed the presence of two main ‘hot’ (HT) and ‘cold’ (CT) tumour immune entities (32.5% and 67.5% of the samples, respectively). In the HT or T-cell inflamed group, the most frequent tumour type was NSCLC (n=47, 29.2%). CT tumours had low expression in T-cell inflammation-related genes. As expected, TILs were significantly higher in the HT group (median 35) than in the CT one (median 5, P value = 0.0018). Interestingly, a subgroup of CT, enriched in CNS tumours (n=40, 23%), showed increased TGFb signaling and presence of TAMs.
Conclusions
Our results indicate that gene expression-based tests, such as VIGex, will aid in tumour microenvironment assessment in FFPE solid tumours.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Oaknin: Honoraria (self), Honoraria (institution): AbbVie, Inc. ; Honoraria (self), Honoraria (institution): Amgen, S.A. ; Honoraria (self): AstraZeneca ; Honoraria (self), Honoraria (institution): Clovis Oncology ; Honoraria (self): F. Hoffmann - La Roche Ltd ; Honoraria (self): Genmab ; Honoraria (self): GlaxoSmithKline SA ; Honoraria (self), Honoraria (institution): Inmunogen ; Honoraria (self): Merck Sharp & Dohme; Honoraria (self), Honoraria (institution): Pharma Mar, SA ; Honoraria (self): prIME ; Honoraria (self), Honoraria (institution): Tesaro; Honoraria (institution): Abililty Pharmaceuticals; Honoraria (institution): Advaxis Inc.; Honoraria (institution): Aeterna Zentaris; Honoraria (institution): Aprea Therapeutics AB; Honoraria (institution): Eisai limited LTD; Honoraria (institution): F. Hoffmann – La Roche LTD; Honoraria (institution): Regeneron Pharmaceuticals; Honoraria (institution): Merck, Sharp & Dohme de España SA; Honoraria (institution): BMS, Bristrol-Myers Squibb. M. Alsina: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Research grant/Funding (self), Travel/Accommodation/Expenses: Merck. E. Elez: Honoraria (self), Honoraria (institution): Hoffman -La Roche; Honoraria (self), Honoraria (institution): Sanofi Aventis; Honoraria (self), Honoraria (institution): Amgen; Honoraria (self), Honoraria (institution): Merck Serono; Honoraria (self), Honoraria (institution): Servier; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Array Pharmaceuticals; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): AbbVie; Honoraria (institution): Pierre Fabre; Honoraria (institution): Novartis; Honoraria (institution): GlaxoSmithKline; Honoraria (institution): Medimmune. T. Macarulla Mercade: Advisory/Consultancy: Shire Pharmaceuticals; Advisory/Consultancy: Roche; Advisory/Consultancy: Batxer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Lilly; Advisory/Consultancy: Ipsen ; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: H3 Biomedicine. C. Saura: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: Genomic health; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Philips Healthwork; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Puma; Advisory/Consultancy: Synthon ; Advisory/Consultancy: Sanofi. J. Capdevila: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Bayer; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Eisai; Research grant/Funding (self): AstraZenca; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): AAA; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Ipsen; Honoraria (self), Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Merk; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Speaker Bureau/Expert testimony: Amgen. M. Vieito: Advisory/Consultancy: Debio; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck-Serono. E. Felip: Advisory/Consultancy: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZenca; Advisory/Consultancy: Blue Print Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: prIME Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: SAMSUNG; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Touchime; Advisory/Consultancy: GSK; Advisory/Consultancy: Bayer; Research grant/Funding (self): Grant for Oncology Innovation (GOI); Research grant/Funding (self): Fundación Merck Salud; Officer/Board of Directors: Grifols. R. Dienstmann: Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony: Ipsen; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Speaker Bureau/Expert testimony: Servier Laboratories; Honoraria (self), Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Research grant/Funding (self): Merck; Research grant/Funding (self): Pierre Fabre. A. Gros: Honoraria (self): Neon Therapeutics; Honoraria (institution): Achilles Therapeutics; Honoraria (self): PACT Pharma; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche Pharma; Licensing/Royalties: Cellular Biomedicine Group, Inc.; Leadership role: Novartis; Leadership role: EMD Serono; Leadership role: Roche Genentech. J. Seoane: Honoraria (self), Research grant/Funding (self), Shareholder/Stockholder/Stock options: Mosaic Biomedicals; Officer/Board of Directors: Northern Biologics; Research grant/Funding (self): Roche Glycart AG; Research grant/Funding (self): Ridgeline; Research grant/Funding (self): Isarna Therapeutics; Research grant/Funding (self): Hoffmann - La Roche, Ltd. P.G. Nuciforo: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Targos Molecular Pathology GmbH. J. Tabernero: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Genentech, Inc.; Advisory/Consultancy: Genmab A/S; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Imugene Limited; Advisory/Consultancy: Inflection Biosciences Limited; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Kura Oncology; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Menarini; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Merus; Advisory/Consultancy: Molecular Partners; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peptomyc; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: ProteoDesign SL; Advisory/Consultancy: Rafael Pharmaceuticals; Advisory/Consultancy: F. Hoffmann-La Roche Ltd; Advisory/Consultancy: Sanofi; Advisory/Consultancy: SeaGen; Advisory/Consultancy: Roche Diagnostics. E. Garralda: Research grant/Funding (self): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Thermo Fisher; Honoraria (self), Leadership role: Roche/Genentech ; Honoraria (self): F.Hoffmann/La Roche ; Honoraria (self): Ellipses Pharma; Honoraria (self): Neomed Therapeutics1 Inc; Honoraria (self): Boehringer Ingelheim ; Honoraria (self): Janssen Global Services ; Honoraria (self): SeaGen; Honoraria (self): TFS; Honoraria (self): Alkermes; Honoraria (self), Travel/Accommodation/Expenses: Bristol-Mayers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Menarini; Leadership role, Travel/Accommodation/Expenses: Glycotope; Leadership role: Agios Pharmaceuticals; Leadership role: Amgen; Leadership role: Bayer; Leadership role: Beigene USA ; Leadership role: Blueprint Medicines ; Leadership role: BMS; Leadership role: Cellestia Biotech; Leadership role: Debiopharm; Leadership role: F.Hoffmann La Roche Ltd ; Leadership role: Forma Therapeutics; Leadership role: Genmab B.V.; Leadership role: GSK; Leadership role: Incyte Biosciences; Leadership role: Incyte Corporation. A. Vivancos: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Sysmex; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Guardant Health; Honoraria (self), Advisory/Consultancy: Bayer; Licensing/Royalties: Ferrer; Honoraria (institution): Debio; Honoraria (institution): Cellestia Biotech; Honoraria (institution): Chittern. All other authors have declared no conflicts of interest.