Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine

// Pierpaolo Correale 1 , Cirino Botta 2 , Nicoletta Staropoli 3 , Valerio Nardone 4 , Pierpaolo Pastina 4 , Cristina Ulivieri 5 , Claudia Gandolfo 6 , Tatiana Cosima Baldari 5 , Stefano Lazzi 7 , Domenico Ciliberto 3 , Rocco Giannicola 1 , Antonella Fioravanti 8 , Antonio Giordano 9 , Silvia Zappavigna 10 , Michele Caraglia 9, 10 , Pierfrancesco Tassone 2, 3, 10 , Luigi Pirtoli 4 , Maria Grazia Cusi 6 and Pierosandro Tagliaferri 3 1 Unit of Medical Oncology, Grand Metropolitan Hospital Bianchi Melacrino Morelli, Reggio-Calabria, Italy 2 Medical Oncology Unit, AUO Mater Domini, Magna Graecia University, Catanzaro, Italy 3 Department of Experimental and Clinical Medicine, Magna Graecia University , Catanzaro, Italy 4 Unit of Radiotherapy, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy 5 Department of Science of Life, Siena University, Siena, Italy 6 Microbiology and Virology Unit, Department of Medical Biotechnology, Siena University, Siena, Italy 7 Unit of Pathology, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy 8 Unit of Rheumatology, Department of Clinical Medicine and Immunologic Sciences, University of Siena, Siena, Italy 9 Department of Biotechnology, Temple University, Sbarro Foundation, Philadelphia, Pennsylvania, USA 10 Department of Precision Medicine, University of Campania L. Vanvitelli, Naples, Italy Correspondence to: Pierosandro Tagliaferri, email: tagliaferri@unicz.it Pierpaolo Correale, email: correalep@yahoo.it Keywords: bio-markers; cancer vaccine; colorectal cancer; K-ras; thymidylate synthase Received: August 24, 2017 Accepted: February 21, 2018 Published: April 17, 2018 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 CD56 dim CD16 bright NKs ( 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.