Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma.

BACKGROUND

Tumor-infiltrating CD8

METHODS

A defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group,

RESULTS

Patients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p<0.05), independent of

CONCLUSIONS

Our results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.

Informations de copyright

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: RB declares patents: (all provisional) PCT/US15/612657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof), PCT/US63/055227 (Methods and Compositions for Treating Autoimmune and Allergic Disorders); JJL declares Data and Safety Monitoring Board: TTC Oncology, Scientific Advisory Board: 7 Hills, Actym, Alphamab Oncology, Array, BeneVir, Mavu, Tempest, Consultancy: Aduro, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Castle, CheckMate, Compugen, EMD Serono, IDEAYA, Immunocore, Janssen, Jounce, Leap, Merck, Mersana, NewLink, Novartis, RefleXion, Spring Bank, Syndax, Tempest, Vividion, WntRx, Research Support: (all to institution for clinical trials unless noted) AbbVie, Array (Scientific Research Agreement; SRA), Boston Biomedical, Bristol-Myers Squibb, Celldex, CheckMate (SRA), Compugen, Corvus, EMD Serono, Evelo (SRA), Delcath, Five Prime, FLX Bio, Genentech, Immunocore, Incyte, Leap, MedImmune, Macrogenics, Novartis, Pharmacyclics, Palleon (SRA), Merck, Tesaro, Xencor, Travel: Array, AstraZeneca, Bayer, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, IDEAYA, Immunocore, Janssen, Jounce, Merck, Mersana, NewLink, Novartis, RefleXion, Patents: (both provisional) Serial #15/612,657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof). SS declares a patent on WNT/β-catenin targeting to enhance anti-tumor immune responses (PCT15/155,099), serves on the SAB on Venn Therapeutics, Tango Therapeutics, Arcus Biosciences and consults for TAKEDA, Replimune, Ribon, Dragonfly and Merck. TFG has received consultancy fees from Merck, Roche-Genentech, Abbvie, Bayer, Jounce, Aduro, Fog Pharma, Adaptimmune, FivePrime, and Sanofi. TFG has received research support from Roche-Genentech, BMS, Merck, Incyte, Seattle Genetics, Celldex, Ono, Evelo, Bayer, Aduro. TFG has intellectual property/licensing agreements with Aduro, Evelo, and BMS. TFG is a co-founder/shareholder of Jounce and Pyxis Oncology. AVD declares Research funding (all to institution for clinical trials): Merck, Roche, Jubilant DraxImage, YMabs, GlaxoSmithKline, Actuate Therapeutics, Lilly; Scientific Advisory Board: Merck; Consultancy: Ology Medical Education; Travel/Accommodations: GlaxoSmithKline; Stock: Pfizer (all outside the submitted work). SLC declares Research funding (to the institution for clinical trials): Merck and United Therapeutics; Stock (personal or immediate family member): United Therapeutics, Merck, Stryker, Amgen, Pfizer, AbbVie, Jazz Pharmaceuticals, Lilly, Sanofi, Varex Imaging, Accelerated Medical Diagnostics, Anthem, Cardinal Health, Novo Nordisk, Regeneron, Zimmer BioMet (all outside the submitted work). The remaining authors declare no competing interests.