@article{3077130,
    title = "Clinical activity of an htert-specific cancer vaccine (Vx-001) in “immune desert” NSCLC",
    author = "Pateras, I.S. and Kotsakis, A. and Avgeris, M. and Baliou, E. and Kouroupakis, P. and Patsea, E. and Georgoulias, V. and Menez-Jamet, J. and Kinet, J.-P. and Kosmatopoulos, K.",
    journal = "Blood cancer journal",
    year = "2021",
    volume = "13",
    number = "7",
    publisher = "MDPI AG",
    doi = "10.3390/cancers13071658",
    keywords = "cancer vaccine;  CD3 antigen;  granzyme B;  immune checkpoint inhibitor;  placebo;  programmed death 1 ligand 1;  telomerase reverse transcriptase;  unclassified drug;  vx 001, aged;  Article;  cancer prevention;  cancer prognosis;  cancer resistance;  cancer survival;  comparative effectiveness;  controlled study;  drug efficacy;  female;  human;  human tissue;  immunocompetent cell;  lymphocytic infiltration;  major clinical study;  male;  multicenter study;  non small cell lung cancer;  overall survival;  prediction;  protein expression;  randomized controlled trial;  tumor associated immune cell;  tumor associated leukocyte;  tumor biopsy;  tumor microenvironment",
    abstract = "Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors. Methods: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low. Findings: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219–0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131–0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11–0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278–0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy. Conclusions: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland."
}