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

July 22, 2022
Source: Oncoimmunology. 2022 Jul 22;11(1):2101596. doi: 10.1080/2162402X.2022.2101596. eCollection 2022.

Authors: Michal Hensler, Jana Rakova, Lenka Kasikova, Tereza Lanickova, Josef Pasulka, Peter Holicek, Marek Hraska, Tereza Hrnciarova, Pavla Kadlecova, Andreu Schoenenberger, Klara Sochorova, Daniela Rozkova, Ludek Sojka, Jana Drozenova, Jan Laco, Rudolf Horvath, Michal Podrazil, Guo Hongyan, Tomas Brtnicky, Michal J Halaska, Lukas Rob, Ales Ryska, An Coosemans, Ignace Vergote, Abhishek D Garg, David Cibula, Jirina Bartunkova, Radek Spisek, Jitka Fucikova.

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 TH2-like signature and immunosuppressive regulatory T (TREG) cells. Clinical responses to DCVAC were accompanied by signs of antitumor immunity in the peripheral blood. Our findings suggest that circulating signatures of antitumor immunity may provide a useful tool for monitoring the potency of autologous DC-based immunotherapy.