Oncotarget. 2018 Apr 17;9(29):20539-20554. doi: 10.18632/oncotarget.24993. eCollection 2018 Apr 17.
Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine.
Correale P1, Botta C2, Staropoli N3, Nardone V4, Pastina P4, Ulivieri C5, Gandolfo C6, Baldari TC5, Lazzi S7, Ciliberto D3, Giannicola R1, Fioravanti A8, Giordano A9, Zappavigna S10, Caraglia M9,10, Tassone P2,3,10, Pirtoli L4, Cusi MG6, Tagliaferri P3.
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.
K-ras; bio-markers; cancer vaccine; colorectal cancer; thymidylate synthase