Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine
- Authors: Correale P.; Botta C.; Staropoli N.; Nardone V.; Pastina P.; Ulivieri C.; Gandolfo C.; Baldari T.C.; Lazzi S.; Ciliberto D.; Giannicola R.; Fioravanti A.; Giordano A.; Zappavigna S.; Caraglia M.; Tassone P.; Pirtoli L.; Cusi M.G.; Tagliaferri P.
- Publication year: 2018
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/512804
Abstract
TSPP is an anticancer poly-epitope peptide vaccine to thymidylate synthase, recently investigated in the multi-arm phase Ib TSPP/VAC1 trial. TSPP vaccination induced immune-biological effects and showed antitumor activity in metastatic colorectal cancer (mCRC) patients and other malignancies. Progression-free and overall survival of 41 mCRC patients enrolled in the study correlated with baseline levels of CEA, immune-inflammatory markers (neutrophil/lymphocyte ratio, CRP, ESR, LDH, ENA), IL-4 and with post-treatment change in p-ANCA and CD56dimCD16brightNKs (p < 0.04). A subset of 19 patients with activating k-ras mutations showed a different immune-inflammatory response to TSPP as compared to patients with k-ras/wt and a worse outcome in term of PFS (p = 0.048). In patients with k-ras/mut, inflammatory markers lost their predictive value and their survival directly correlated with the baseline levels of IL17/A over the median value (p = 0.01). These results provide strong hints for the design of further clinical trials aimed to test TSPP vaccination in mCRC patients.