@article {44711,
	title = {Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC},
	journal = {Cancers},
	volume = {13},
	number = {7},
	year = {2021},
	note = {Pateras, Ioannis SKotsakis, AthanasiosAvgeris, MargaritisBaliou, EvangeliaKouroupakis, PanagiotisPatsea, EleniGeorgoulias, VassilisMenez-Jamet, JeanneKinet, Jean-PierreKosmatopoulos, KostasengSwitzerland2021/05/01 06:00Cancers (Basel). 2021 Apr 1;13(7):1658. doi: 10.3390/cancers13071658.},
	month = {Apr 1},
	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 naive 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 \&lt; 0.001, HR = 0.279, 95\% CI 0.131-0.595), CD8-TIL low (21 vs. 6.6 months, p \&lt; 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.},
	keywords = {All remaining authors have nothing to disclose., cancer vaccines, granzyme B, immunologically cold tumors, metastatic non-small cell lung cancer, shareholder of Vaxon Biotech. K.K. and J.P.K. are shareholders of Vaxon Biotech., tumor-infiltrating lymphocytes, Vx-001},
	isbn = {2072-6694 (Print)2072-6694 (Electronic)2072-6694 (Linking)},
	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.}
}
