Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines.

Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts. We performed biomolecular and cytofluorometric analyses on peripheral blood samples collected prior to immunotherapy from 1000 patients enrolled in these trials, with the objective of identifying immunological biomarkers that may improve the clinical management of DCVAC-treated patients. Gene signatures reflecting adaptive immunity and T cell activation were associated with favorable disease outcomes and responses to DCVAC in patients with prostate and lung cancer, but not ovarian carcinoma. By contrast, the clinical benefits of DCVAC were more pronounced among patients with ovarian carcinoma exhibiting reduced expression of T cell-associated genes, especially those linked to T

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© 2022 Sotio Biotech. Published with license by Taylor & Francis Group, LLC.

Déclaration de conflit d'intérêts

IV declares consulting for AstraZeneca, Clovis Oncology Inc., Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, F. Hoffmann-La Roche Ltd, Genmab, GSK, Immunogen Inc., Jazzpharma, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology NV, Oncoinvent AS, Sotio a.s., Verastem Oncology, Zentalis; contracted research for: Oncoinvent AS, Genmab; and research funding from Amgen and Roche. RS and JB are minority shareholders of Sotio. ADG received fees for consultancy, lectures or services from Boehringer Ingelheim (Germany), Miltenyi Biotec (Germany), Isoplexis (USA) and Novigenix (Switzerland). AR declares advisory services and invited lectures for Amgen, AstraZeneca, BMS, Eli-Lilly, Janssen-Cilag, MSD, and Roche. AC is a contracted researcher for Oncoinvent AS and Novocure and a consultant for Sotio Biotech a.s. MH, JR, LK, TL, JF, PH, MH, TH, PK, KS, DR, LS, JB, RS, and JF are employees of Sotio a.s. The other authors declare no conflicts of interest.