Cell-Mediated Immunity Induced By Active Immunotherapy In Non Small Cell Lung Cancer Patients Vaccinated With Racotumomab

SEGATORI VALERIA INÉS; HÉCTOR CUELLO; ALBERTÓ MARINA; GULLINO C; ALONSO DANIEL F; GABRI MARIANO R

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedada Argentina de Investigación Clínica

In cancer, altered expression of glycoenzymes (GE) results in cell surface glycosylation changes, such as falling or rising expression of certain glycans, accumulation of precursors and appearance of incomplete and novel structures. The resulting altered glycophenotype (GP) is a leading factor in the behavior of the transformed cell, having a crucial role in the development of the malignant phenotype. Little is known about the GP in pediatric cancers such as Neuroblastoma (NB), Retinoblastoma (RB), and Medulloblastoma (MB). The aim of this work is to characterize the GP in pediatric cancers and its relationship with the GE transcripts levels in cell lines and in Patient´s Derived Primary Tumor Cell Cultures (PDTCC). GP was evaluated by the detection of terminal glycans by flow cytometry using monoclonal antibodies against LeX, SLeX, LeA, SLeA, LeY, LeB, Tn, T, and the branching characterization using lectins. Transcripts levels of GE were measured by Real-Time PCR with specific primers. Results showed that expression of Lewis glycan family is related to an aggressive tumor GP. We observed high expression of SLeX and Lex in RB Weri-RB1 cell line, which is in accordance with high transcripts levels of ST3Gal3 and C2GnT1. However, Y79 cell line showed a lower or an absent expression of these glycans as well as the related GE. Whereas N-myc amplified NB cell line CHP-212 expressed high levels of SLeX, SleA and LeY, as observed in other N-myc amplified NB cell lines, N-myc non amplified cells did not show these GP. While evaluating metastatic MB PDTCC, we observed that high expression of SLeX occurred in accordance with high levels of ST3Gal3 and C2GNT1 transcripts. We propose that tumor cell lines could be a useful tool to resemble the patient´s tumor GP. Also, regarding the few reports related to the GP and GE expressions in pediatric tumors, our results suggest that there is a substantial modulation of them in relation to the aggressiveness of the cells.